| 00:02 | is that this is a neuroscience lecture and it's october 13th thursday. Uh |
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| 00:14 | actually will not get into CNN yesterday we will finish neuro transmission. I |
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| 00:21 | we had maybe about half an hour minutes left. But I did this |
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| 00:25 | yesterday and it took me a little over an hour. And so we |
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| 00:30 | with Tuesday I mean monday Wednesday section stop at the neuro transmission. Uh |
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| 00:39 | have your quiz one on monday okay you can see it on casa it's |
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| 00:49 | same online monitored just like you did it's 10 minutes it's going to be |
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| 00:58 | questions. Those questions are going to on your transmission 123 and today four |
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| 01:07 | . There's a lot of details in lecture I think and you can expect |
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| 01:15 | some of the questions will have greater of detail on the systems that we've |
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| 01:22 | in greater detail or repeated discussing several and more general questions potentially on some |
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| 01:30 | the other things that we didn't spend much time cover early. But basically |
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| 01:35 | three lecture notes So it's about 23 34224 questions per each one of these |
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| 01:43 | . Now as you can imagine. so please register for your time slots |
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| 01:51 | just 10 minutes and have your equipment quiet spot and your I. |
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| 01:57 | S. And it's just too much the material you have the whole weekend |
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| 02:03 | video online and then hopefully you can the quiz especially those that I see |
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| 02:10 | all the time and that will help with your exam scores if you did |
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| 02:15 | do as well as you wanted Okay so for the past two |
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| 02:23 | 23 lectures actually we have been discussing neurotransmitter systems and we talked in great |
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| 02:33 | but glutamate and gaba system and we'll even more about that. Today we |
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| 02:40 | the dramaturgical signaling last lecture through an . D. A. And AMP |
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| 02:44 | receptor and we'll cover that in great . Will also look at how Gaba |
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| 02:50 | through both and the tropic gaba and tropic gaba B receptors. Uh acetylcholine |
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| 02:57 | we see in the brain binds to the tropic nicotine IQ and metabolic tropic |
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| 03:05 | receptors. So this mean is different serotonin and the means and also from |
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| 03:11 | means because serotonin enemies and cata cola will all be acting through metal tropic |
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| 03:18 | protein coupled with separate systems. You know everything about acetylcholine, you should |
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| 03:25 | how it synthesized, how it's degraded the synapse can be transported back into |
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| 03:32 | pre synaptic terminal and re synthesized. these are great questions that are typically |
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| 03:39 | on the exam, on the synthesis breakdown of acetylcholine or what mechanism of |
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| 03:46 | . Uh common alzheimer's medications have, talking about Alzheimer's yesterday there was some |
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| 03:55 | interview. Some new drug is coming of Japan that slows down the progression |
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| 03:59 | 27% that's clinically significant. So just give you an idea of what what |
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| 04:07 | out on the market is something that slow down the progression. 20-30% of |
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| 04:13 | disease is a clinically significant drug clinically effect. But it's still not a |
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| 04:20 | . It's basically slowing down the progression the onset of severe alzheimer's. So |
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| 04:26 | will, as I mentioned, this calling function through receptors they have their |
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| 04:32 | agonists and antagonists. Um Mascara nick will have an opposing action to nicotine |
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| 04:41 | . Nicotine receptor will let in sodium potassium but the influx of sodium through |
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| 04:50 | receptor channel, this is nicotine receptor of sodium initially through this channel and |
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| 05:00 | e flux of potassium with this initial of sodium will cause a small deep |
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| 05:07 | for synoptic deep polarization. So if acetylcholine binds to metabolic tropic, |
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| 05:18 | acetylcholine G protein coupled receptor, that is going to activate G protium which |
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| 05:29 | open potassium channel and potassium is going be leaving the cell and positive |
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| 05:38 | Leaving the cell will cause the hyper here small hyper polarization. So it's |
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| 05:44 | same molecule that nicotine nick will lead small deep polarization. Most chronic which |
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| 05:52 | act through what is called the shortcut because there are no chemical into media |
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| 05:56 | between the receptor and the G There's no other enzyme. There is |
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| 06:03 | of the secondary messenger chinese adjust the protein complex catalytic subunit will cause the |
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| 06:09 | of potassium generals. We'll come back this. But the same principle follows |
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| 06:16 | cata cola means you don't need to the intermediaries and the enzymes that are |
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| 06:23 | in synthesis of the cattle colonies. what you should know is you should |
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| 06:29 | some of the uh signaling for Nora formidable tropic signaling which will look |
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| 06:36 | And that is the general principle of colonies being cycled from the sent out |
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| 06:41 | into the pre synaptic terminals reloaded, synthesized or broken down in this case |
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| 06:47 | would be broken down by M O. Mon. I mean oxide |
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| 06:53 | in the present active terminals and the theme of if you want to affect |
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| 07:01 | , if you want to prolong the availability of neurotransmitters, you can block |
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| 07:06 | transporters in this case of that neurotransmitter that's another pharmaceutical strategy to now. |
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| 07:14 | tona is involved in mood, sleep and learning. And in the |
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| 07:20 | slide cattle colonies are also involved in . And so you have to think |
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| 07:26 | maybe different types of mood to like , sleepy mood, happy mood versus |
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| 07:34 | mood alert mood. These are different of being a different moods in a |
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| 07:39 | . So I took this time as precursor to five http which is a |
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| 07:45 | to serotonin and common antidepressant drugs would the serotonin re uptake by blocking the |
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| 07:55 | for serotonin and there are also mono oxidase inhibitors and by inhibiting modern mean |
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| 08:03 | , you can again prolong and have of that molecule available from prison ethically |
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| 08:09 | this case. Um So we looked this system here and we said okay |
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| 08:15 | you have the same molecule and the molecule through the tropic perception can be |
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| 08:22 | D polarizing on membrane potential and through tropic receptor it's hyper polarizing to the |
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| 08:28 | , the membrane potential. So what the systems that act only through medical |
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| 08:33 | receptors? What about norepinephrine which only through G protein coupled receptors? Can |
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| 08:39 | be opposing actions? And what are opposing actions? Were not looking now |
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| 08:44 | you look at these things here these there really cellular molecular mechanisms and activation |
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| 08:53 | secondary messengers. Some kindnesses which will for a late will add P. |
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| 08:58 | . For group and they're also foster which will defense for like molecules. |
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| 09:04 | there's the whole world of these secondary and what we call it a cellular |
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| 09:10 | cascades because the cascade out and they diverge or they can converge on the |
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| 09:16 | molecule with norepinephrine and there are two of receptors that are quite common beta |
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| 09:24 | alpha beta is linked to GS which a stimulator, G protein which will |
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| 09:32 | and all cyclist and will produce cyclic and will promote production of protein, |
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| 09:38 | say and alpha two receptors linked to . I and inhibitor G podium and |
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| 09:46 | of G. I will inhibit the cyclists and inhibit production of and so |
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| 09:54 | athletes follow the push pathways pushing to more of this protein primates and this |
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| 10:00 | the full path in a way it's the system away from producing more of |
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| 10:06 | secondary messenger P. K. A . Chinese says A is A. |
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| 10:12 | an enzyme but kindnesses can force for late again. They can add three |
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| 10:18 | four groups to receptors and to other and they can influence the uh their |
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| 10:25 | . So recall that amines are very in the sense that they are expressed |
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| 10:32 | very specific locations and very specific nuclear the brain. They're different from amino |
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| 10:38 | and different from peptides that are more distributed and expressed and cells can co |
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| 10:44 | neural peptides and amino acids but the neurotransmitters if you were to take out |
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| 10:52 | remove Lucas. So really is this which contains the stillness of neurons that |
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| 10:57 | capable of synthesizing more as if you just removed this nucleus. The brain |
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| 11:03 | not have more of. So that synthesis system is here and what I |
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| 11:10 | the non specific sprinkler system. This with projections are the synapses and the |
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| 11:17 | that commodity cells and synapses throughout the , widely very spatially distributed throughout the |
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| 11:24 | and sub cortical areas. So it's probably good to know that locus |
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| 11:30 | produces norepinephrine that rafi nuclei produce serotonin that you have two nuclei and that's |
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| 11:38 | I typically don't ask you maybe the because magna cellular basal forebrain produces a |
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| 11:45 | Colin. And then the gun killer and lateral. Also segmental nuclei here |
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| 11:53 | a so uh so it's a difficult here. Typically don't ask for these |
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| 12:00 | of the nuclei for acetylcholine but it's easy to remember raph and local civilians |
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| 12:06 | these other. I mean so just that there are two places and that |
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| 12:10 | is this frontal basil board brain found spot where Siegel Colin is produced. |
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| 12:25 | . And the cannabinoids are different and cannabinoids and I also have in parenthesis |
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| 12:31 | nitrous oxide and carbon monoxide. Because of the features that we discuss about |
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| 12:36 | cannabinoids applied to the gasses like And there's several things here when we |
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| 12:43 | about neural transmission here, we're talking amino acids being released, they released |
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| 12:53 | the cannabinoids produced personality and release parson . So this pre synaptic synaptic signaling |
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| 13:02 | referred to as interrogated and this Remember these molecules are not stored in |
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| 13:08 | they will diffuse through the membranes and will essentially travel and bind to where |
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| 13:14 | find the receptors and their receptors CB receptors. One are ubiquitously expressed on |
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| 13:21 | pre synaptic terminals of both the inhibitor excitatory south and by activating this activation |
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| 13:29 | post synaptic synaptic is referred to as and by activating the CB one receptor |
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| 13:36 | will activate the g protium which will the calcium channel, voltage gated calcium |
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| 13:43 | and in the absence of calcium there be a reduction in particular fusion in |
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| 13:48 | transmitter luiz and cylinder. Cannabinoids control do polarization, do suppression of inhibition |
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| 13:56 | they control the release of excitation and get engaged when there are heightened levels |
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| 14:02 | activity. When there is a potentially and stressful levels of activity in neurons |
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| 14:08 | even other cells in the body. it's moderate to severe stress, the |
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| 14:14 | engagement you will see in this system can think of it as a negative |
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| 14:18 | system or retrograde signaling system. Either CB one receptors are dominating on neurons |
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| 14:26 | CB two receptors cannabinoid receptors to are on glial cells. And we'll talk |
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| 14:32 | this later. And of course when talk about them the cannabinoid system in |
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| 14:35 | detail. The two endogenous accepted and endocannabinoid anandamide and two ag phenomenal |
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| 14:45 | The exogenous of the phyto cannabinoid that shown here will also find the suffers |
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| 14:53 | THC is find in the plants. phyto cannabinoid tetrahydrocannabinol delta line is a |
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| 15:03 | phyto cannabinoid which is found in the . And then there are synthetic cannabinoids |
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| 15:08 | can be quite dangerous. And there some out on the market. Delta |
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| 15:12 | TH C. Which is a synthetic made from either DELTA nine or from |
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| 15:18 | . Non psychotropic cannabinoid called CBD or and you will see a lot of |
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| 15:24 | for delta Aid. Because this market cannabinoid cannabinoid market and synthetic cannabinoid market |
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| 15:31 | it's quite complex and it's regulated and some instances it's unregulated by states |
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| 15:39 | So these are the most important And nitrous oxide. Carbon monoxide will |
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| 15:43 | have present optic receptors. It will function in this retrograde fashion and will |
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| 15:48 | have the vesicles and the membrane Okay so when we come to glutamate |
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| 15:56 | Gaba remember that the major inhibitory neurotransmitter is made from glutamate. So all |
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| 16:02 | the inhibitory cells inhibitory interneuron that release . They should have God Tommy Cassidy |
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| 16:09 | slates which takes away this acid group turns glutamate into Gaba adds a charge |
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| 16:17 | . So if we go back a slides I think I misplaced a couple |
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| 16:23 | slides. This one in particular what's and glutamate signaling is that we think |
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| 16:31 | glutamate signaling and in general the synaptic between neurons as very much uh influenced |
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| 16:41 | and controlled by glial cells. And we refer to the synopsis is tripartite |
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| 16:47 | part one neuron. Pre synaptic neuron to post synaptic neuron part three glial |
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| 16:54 | and after gliding it gets released it to anna tropic and medical tropic |
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| 17:00 | Glutamate will get transported back through glutamate transporters back into pre synaptic terminals and |
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| 17:07 | back into bicycles for subsequent release. glial cells and in particular ostracized will |
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| 17:15 | glial glutamate transporters and they will pick a lot of these glutamate and glutamine |
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| 17:22 | that they have inside of them will it into glutamine and they will share |
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| 17:27 | is glutamine with neurons and neurons with help of another enzyme glue laminates and |
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| 17:34 | energy will turn it into glutamate and back into the vesicles. So by |
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| 17:39 | virtue you can imagine that if there a dysfunction and glial glutamate transporters that |
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| 17:45 | affect the amount of glutamate that is the synapse and how much it is |
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| 17:49 | cleared. And so we see that cells can actually be involved in in |
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| 17:54 | serious pathologies by having damage to these proteins like the glutamate. And it |
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| 18:01 | tells you that glia in a way a say of how much glutamate this |
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| 18:07 | has and how much of it can re synthesized and re released. So |
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| 18:13 | why I refer to it as a synapse. Uh We called it just |
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| 18:19 | glutamate will have its own transporters. will have its own transporters into the |
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| 18:23 | synaptic terminals and then specific transporters into vesicles also. And then we ventured |
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| 18:29 | just starting to talk about the details glutamate. Ergic neural pharmacology neurophysiology. |
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| 18:38 | are three types of iron. A intimate receptors. Three subtypes amp A |
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| 18:43 | M. D. Anti made. have their own respective chemical agonists and |
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| 18:48 | have their own respective chemical antagonists and talk from the second when glutamate gets |
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| 18:54 | post synaptic lee generates an E. . S. P. So we |
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| 19:02 | the neuro muscular junction with the central system synopsis and we said that central |
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| 19:08 | system synopsis E. P. P. S. Are small and |
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| 19:12 | you have activation of multiple excitatory fibers have a larger ep sp response. |
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| 19:20 | so when you release neurotransmitter in this we're releasing glutamate. This is |
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| 19:28 | Does glutamate. Okay now post synaptic the release of this bulletin made by |
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| 19:37 | to this post synaptic cell it's going generate. This is our glutamate release |
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| 19:44 | stimulation and with a little bit of delay for this automated travel and bind |
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| 19:50 | the respective receptor channels and G protein receptors here we're gonna have an |
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| 19:56 | P. Sp response. Okay this excitatory post synaptic potential or E. |
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| 20:02 | . S. P. And this . P. S. P. |
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| 20:05 | delay synaptic delay can be anywhere around milliseconds let's say and duration of the |
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| 20:12 | . P. S. P. anywhere between their shorter E. |
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| 20:17 | S. P. S. And longer E. P. S. |
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| 20:19 | . S. But let's approximately 20 in duration. So they're much longer |
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| 20:27 | for synaptic potentials in the action So we discussed in the first section |
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| 20:31 | the sports that were only one milliseconds duration and very large amplitude. Those |
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| 20:37 | external. So the initial phase and D. Polarization of this E. |
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| 20:44 | . S. P. Comes through of ample channels. When glutamate gets |
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| 20:50 | . Pre synaptic alie you can bind geographically in Tampa and and then via |
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| 20:58 | . And when it binds to ample immediately opens up receptors. But when |
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| 21:02 | binds to N. M. A receptor it doesn't open. And |
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| 21:05 | the receptor channel because the channel is up with magnesium. So there's an |
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| 21:11 | . D. A receptor has a site for magnesium and the magnesium is |
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| 21:15 | going to leave the channel and open up if there is a deep polarization |
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| 21:22 | resting membrane potential to some more positive minus 40 minus minus 15 minus 30 |
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| 21:29 | bowls. And that's when you open the N. M. D. |
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| 21:32 | receptor channel all of the instances and the receptors to go to conduct sodium |
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| 21:39 | and calcium influx of calcium is significant . Not for the number of potential |
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| 21:45 | but calcium inside the south is like secondary messenger too. And only some |
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| 21:52 | receptors will be permissible. 2000 most them will be permissible. Just the |
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| 21:57 | and potassium but some of them and see what the differences are permeable to |
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| 22:04 | . So ampaTA receptors and protein receptor will conduct about 20 pickers, demons |
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| 22:13 | M. D. A. Receptor about 50 people seaman's which means that |
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| 22:16 | a much larger conductance channel. It a little bit for it to open |
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| 22:20 | deep polarization. But when it opens conducts a lot of ions am picky |
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| 22:26 | will be blocked by C. Q. X. It's an antagonist |
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| 22:31 | then M. D. A receptor will be blocked by a PV. |
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| 22:35 | that will show up again in uh couple of slides. A PV or |
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| 22:41 | P five used interchangeably and M. . A receptor is referred to as |
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| 22:46 | detector. It has to coincidentally detect pre synaptic neurotransmitter release which is glutamate |
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| 22:55 | the post synaptic deep polarization which comes the activation of the ample channels |
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| 23:02 | So it is if there's just NMDA receptor is not going to build |
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| 23:07 | if there's just deep polarization no present activation and M. D. A |
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| 23:11 | is not going to open. It both needs neurotransmitter and it needs deep |
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| 23:17 | and in addition to needing that neurotransmitter seen another amino acid. It serves |
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| 23:22 | a co factor which means that lie is necessary for this glutamate as a |
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| 23:28 | factor to initiate the opening of an . D. A receptor channel in |
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| 23:34 | spinal cord. We studied licensing in spinal cord inter neurons is the major |
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| 23:40 | in neurotransmitter. And here glycerine is co factor that influences post synaptic an |
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| 23:46 | . D. A receptor. Excitatory . So all of these are different |
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| 23:52 | and NBA receptors has different sides remember a complex structure, it's a three |
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| 23:59 | structure also when the channel opens the changes its confirmation it changes its three |
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| 24:07 | structure. It literally moves right. conformational change in these protein channels. |
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| 24:13 | of the gates opening of the And so some of the molecules that |
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| 24:19 | shown here in magnesium actually has two side, zinc even has a binding |
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| 24:25 | here, there is a mention of molecule MK 80. A M K |
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| 24:30 | to 1. It's an M. . A receptor antagonist, but only |
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| 24:35 | an M. D. A receptor open. So a PV will block |
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| 24:40 | M. D. A receptor no what. But M K 801 will |
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| 24:47 | block NMDA receptors once they're open. can this happen if you change the |
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| 24:54 | of this large three dimensional protein structure all of these are different crevices where |
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| 25:00 | interactions with I mean asset sequences and proteins where these molecules combined. So |
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| 25:07 | you change the confirmation of this complex dimensional structure, you create new |
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| 25:13 | new potential areas and binding sites where other molecules can come in and bind |
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| 25:20 | as M. K. Don't wants M. D. A receptor is |
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| 25:23 | , it won't bind to it and . D. A receptor is |
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| 25:26 | That means there's a new binding site opened up and it will bind to |
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| 25:31 | molecules will compete for the same That means that they have this key |
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| 25:37 | that fits the lock and there's two that can fit the lock. |
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| 25:43 | so those are called competitive agonists or antagonists will be competing for the same |
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| 25:49 | and sometimes substances have different locations where mind too. So they're not competing |
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| 25:54 | each other in that case there noncompetitive or antagonists uh and then via receptor |
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| 26:00 | a binding side for PCP uh which another, the street name is crystal |
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| 26:11 | , think it's also called Angel Dust lot of times it's an illicit street |
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| 26:16 | . And the reason why I pointed here is because there are certain things |
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| 26:21 | are out in nature like cannabinoids for , that human bodies interact with these |
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| 26:29 | cannabinoid molecules. And the cannabinoids of is endogenous phyto cannabinoid molecules will interact |
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| 26:36 | our endogenous systems. Right. And fairly safe meaning that there is no |
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| 26:44 | or some crazy things that are happening some of the botanical preparations that are |
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| 26:50 | there including the fifth Economicas. there's stuff out there, especially synthetic |
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| 26:58 | and as we know, there is huge problem with opioids that is happening |
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| 27:02 | this country and sentinel, which is strong. Opioid and opioid system is |
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| 27:08 | sensitive, meaning that when you think the drugs or these systems in which |
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| 27:13 | drugs act, you're thinking about neurotransmitter , cata colon and serotonin. It's |
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| 27:19 | . Some of these systems have an dose which means that opioids are used |
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| 27:25 | pain effectively it will block the pain this does but three times as does |
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| 27:32 | kill you and then there are substances have an effective dose that is potentially |
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| 27:41 | and the lethal dose that is sometimes hard to achieve to die from certain |
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| 27:47 | of course there are all sorts of . Extraneous circumstances and PCP what it |
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| 27:53 | do besides inducing hallucinations. It can produce. It's a free nia from |
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| 28:00 | single or few time useless. It people into psychosis and it can give |
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| 28:07 | sustained chronic schizophrenia. So some of systems that very sensitive and that's why |
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| 28:14 | always say that synthetic things. I my kids if it stinks like if |
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| 28:20 | smells then you kind of know what is. You know you smell |
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| 28:24 | it's poop you know but if you smell anything and it's all synthetic, |
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| 28:30 | don't really know what it is and it comes from and how it interacts |
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| 28:35 | these different systems and it can be dangerous. Okay. And then the |
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| 28:39 | receptor here then is implicated in some these very major changes that can happen |
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| 28:45 | upsetting the system. This is an of things that you have learned in |
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| 28:52 | course you have learned about the voltage , you have learned about the currents |
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| 28:59 | now we're gonna live here in this . There is release of glutamate and |
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| 29:04 | have 1.2 mil imola magnesium on this and zero magnesium on this side. |
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| 29:12 | $1.2 million magnesium is a normal magnesium . Alright. But zero magnesium is |
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| 29:22 | there is no magnesium extra cellular available that is an experimental condition. So |
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| 29:29 | physiologically if you are now isolated in occurrence because you have voltage clamp, |
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| 29:35 | have pharmacology, you block damper you're just looking at an M. |
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| 29:39 | . A. Current, you apply and you can see that an |
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| 29:43 | B. A currency's downward deflections are going to be active much with minus |
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| 29:48 | million bowls. But you can see there's a lot of current flocks starting |
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| 29:53 | happen and more D. Polarized Zero mila bowls and M. |
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| 29:59 | A receptor current reverses. There's no . There's zero currently zero knowable. |
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| 30:09 | when we talked about iron channels we about the equilibrium potential and I said |
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| 30:20 | potential is calculated for individual ions E D N. A E C. |
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| 30:32 | . And so right. The equilibrium for different lines. And that equilibrium |
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| 30:37 | value minus 19 million balls or positive million balls and so on. We |
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| 30:44 | that the currents reverse right. But we're looking at an M. |
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| 30:50 | A receptor channel and an M. . A receptor doesn't have an equilibrium |
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| 30:58 | because equilibrium potential is calculated or single species. And and M. |
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| 31:05 | A receptor is we just looked at allows sodium to come in calcium to |
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| 31:14 | in and potassium to leave. So it actually tells you that |
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| 31:26 | This is where the reversal potential for ion species, sodium calcium potassium reverse |
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| 31:33 | an engineer. Because now we're looking three ionic species traveling through one |
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| 31:40 | Right? Because it's zero million balls can see that it prefers to conduct |
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| 31:47 | really. And because it has calcium is positive 125 mila bowls, it's |
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| 31:55 | toward these positive ions the reversal So it reverses a zero. And |
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| 32:01 | at positive potentials you can see that M. D. A. Receptor |
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| 32:06 | 60 conducts way more current than the 60 that actually prefers to conduct |
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| 32:12 | And in the years after what happens you remove magnesium, if you remove |
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| 32:18 | and you have zero magnesium Then at million balls in the presence of |
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| 32:25 | You see very large current stone D. A receptor. Okay. |
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| 32:31 | they reverse it zero and you can strong currents and the positive potentials |
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| 32:37 | So what this experiment shows is that is indeed blocking an M. |
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| 32:42 | A receptor. And if you remove in the presence of NMDA receptors will |
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| 32:49 | opening even at these hyper polar But also shows that the reversal potential |
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| 32:56 | an M. D. A receptor zero mila bowls. So you know |
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| 33:01 | else reverses at zero million volts ampara M. B. A. Which |
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| 33:10 | E. P. S. Speed also E. P. P. |
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| 33:16 | played potential In the neuro muscular junction reverses at zero millennials. So this |
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| 33:25 | this is all of the zero million that that that E. P. |
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| 33:30 | . P. S, ample and . D. A. And athlete |
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| 33:34 | . So versus zero million balls earlier the stores. We looked at the |
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| 33:39 | plots. I for current negative current N. Word positive current is |
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| 33:49 | V. For voltage numbering boulders. we are smart because we have learned |
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| 33:57 | several interesting techniques and what we have is an experimental setup in the city |
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| 34:06 | per second. If you don't mind setup in which you're stimulating or you're |
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| 34:17 | glutamate, you're stimulating this this this here that you're seeing throughout is when |
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| 34:23 | stimulus happens and then a couple of later there's a response. And in |
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| 34:31 | experiment you have a voltage clamp that using at minus 80 minus 40 million |
|
| 34:38 | and plus 20 million volts. And you clamp a different membrane potential to |
|
| 34:45 | the same stimulation in your recording these . You have two time slots where |
|
| 34:53 | measuring the current. You're measuring the p current. Only a few milliseconds |
|
| 35:00 | the stimulation. This is the first line and then you're measuring the late |
|
| 35:08 | about 20 milliseconds later. This is time scale here, 50 millisecond bar |
|
| 35:15 | 20 milliseconds later you have a second line and you're measuring how much current |
|
| 35:20 | still there 20 milliseconds later Or is late current what we call. So |
|
| 35:27 | measure the early component of minus 80 40 0 2040 and this is the |
|
| 35:35 | . M. D. A And when you I'm sorry this is |
|
| 35:38 | early non N. M. A component which is really ample |
|
| 35:45 | And this I. V. Plot in the triangles and it is linear |
|
| 35:51 | it shows that it has linear B with the reversal potential zero Millersville. |
|
| 35:58 | these are early currents here and occurrence non N. M. D. |
|
| 36:03 | . And they have the linear B plot. However, when you |
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| 36:09 | the amount of current at the second line which is late current that -80 |
|
| 36:17 | barely see any of that late current to this early currently is a lot |
|
| 36:23 | late current. There isn't much at 40. This blue area under the |
|
| 36:29 | it's all an M. D. current and it's all late current. |
|
| 36:32 | you can see the difference between here there is much greater at minus |
|
| 36:37 | So you do have a significant late there and you have a significant late |
|
| 36:44 | positive potentials. So I. Plot for an M. D. |
|
| 36:48 | receptor channel. Are these closed or circles At -100 -80. There isn't |
|
| 36:57 | activity as you d polarize the there's more current coming in and then |
|
| 37:03 | start going to more positive potentials. reverses the General Miller balls and it |
|
| 37:08 | to want to conduct a lot in outward direction. So this is the |
|
| 37:14 | . M. D. A receptor currents of these filled circles showing that |
|
| 37:21 | is a nonlinear I. V. . Remember I drew this crazy diagram |
|
| 37:27 | I said imagine all of these ivy with all of their curves and reversals |
|
| 37:32 | this is what makes ourselves by physically and what makes them in different |
|
| 37:37 | So now you're seeing how the same PSP components. That early component is |
|
| 37:45 | component. The late component of that . P. S. B. |
|
| 37:48 | a nonlinear the curve. Uh And these open circles and these open triangles |
|
| 37:59 | in this experiment. Do you apply pD which is an M. |
|
| 38:04 | A. Receptor antagonist? And what is that this bottom line here is |
|
| 38:12 | a PV. And this top line a with with a PV. So |
|
| 38:17 | antagonist will essentially block the entire blue under the curve. But it is |
|
| 38:25 | going to affect anything about the early because an M. D. A |
|
| 38:30 | antagonist is specific to an M. . A receptor. You specifically blocking |
|
| 38:35 | late component. When you block the component, you get these open circles |
|
| 38:40 | it's essentially flatline hovering around zero There's no current but it does not |
|
| 38:48 | the early component. So the key from the slide is you have linear |
|
| 38:55 | . V. Plot for ampara nonlinear . V. Plot for an |
|
| 38:59 | B. A. That you can the early p currents that are representative |
|
| 39:05 | AMP A. And late currents 20 later that are representative of an |
|
| 39:10 | D. A. And that you use these techniques like voltage clamp a |
|
| 39:15 | pharmacology to isolate study the properties of plots and uh study the currents and |
|
| 39:23 | dynamics. So this is another really part that I alluded to. As |
|
| 39:30 | said that calcium permeability and amping. several important topics in this slide calcium |
|
| 39:39 | ini which is development and cellular We'll talk about that in a |
|
| 39:46 | Calcium permeability and amping receptors. I only some ample receptors will be permeable |
|
| 39:52 | calcium. Now let's look at It turns out that there are subunits |
|
| 39:59 | the ample receptor. Well you look little bit about the structure later and |
|
| 40:02 | have trans membrane segments. Trans membrane in this case are M segments. |
|
| 40:08 | look at s trans membrane segments in gated sodium channels. This is M |
|
| 40:15 | segments And this is a sequence from segment of Amino acids that contains Cube |
|
| 40:23 | is glutamine and the edited sequence which of the amino acids will have. |
|
| 40:29 | edited sequence substitutes Q. With an . Which is argentine and by changing |
|
| 40:39 | single amino acid you have the receptor not conducting calcium to conducting calcium. |
|
| 40:50 | that is significant because I said calcium not in this case. We're not |
|
| 40:55 | at deep polarization through calcium posson optical looking at the activity of calcium inside |
|
| 41:01 | cells and secondary messengers through these intracellular cascades. So analogy of that that |
|
| 41:09 | used and I'm not sure if it very effective but let's say there are |
|
| 41:14 | elevators in the building and it's a building, huge building with different components |
|
| 41:22 | . C. Units and you know of bricks that built it and you |
|
| 41:27 | up to the side of the building you withdraw one brick and two elevators |
|
| 41:32 | working Only three out of five for you just removed one brick. So |
|
| 41:40 | is an analogy of substituting a single acid in this complex massive three dimensional |
|
| 41:47 | and all of a sudden the channel allow for calcium permeability. And in |
|
| 41:54 | experiment you have the cue so you glutamate and you measure sodium currents. |
|
| 42:01 | apply glutamate and you measure calcium But when you have the R. |
|
| 42:08 | you apply glutamate and you get still sodium currents. But there is no |
|
| 42:14 | calcium currents going through it. So can prove it experimentally. You can |
|
| 42:18 | it experimentally with the current recordings. interesting that during early developmental stages neuronal |
|
| 42:28 | predominantly express an M. D. receptor. Some synapses solely expressing |
|
| 42:35 | D. A receptors. And those are referred to as silent synopsis. |
|
| 42:41 | that an M. D. A opens following ample activation. And if |
|
| 42:46 | don't have am put in the That means there is another way that |
|
| 42:51 | synapse has to de polarize significantly in for an M. D. A |
|
| 42:55 | to open. So they're called silent . Because even if glutamate is being |
|
| 43:00 | prison optically there's no pasta no haptic to an M. D. A |
|
| 43:06 | . So something else is happening That's typically very large influxes of calcium |
|
| 43:12 | allow for post synaptic deep polarization and of these receptors. And M. |
|
| 43:18 | . A receptor is also have sub . So all of these are different |
|
| 43:23 | units and then M. D. receptor is there and our sub units |
|
| 43:29 | A. Two B one A one . And I don't want you necessarily |
|
| 43:35 | know this detail except that during the the profile of the subunits and the |
|
| 43:41 | composition of these channels may change. during the development you may have an |
|
| 43:47 | a dominating compared to enter to be and then the ratio of the snR |
|
| 43:54 | in order to be subunits may change the adulthood. So it's a dynamic |
|
| 44:00 | too cellular location and activity dependence. we understand that an M. |
|
| 44:07 | A receptor because it's a coincidence detector actually in a perfect position to be |
|
| 44:13 | for plasticity and can mediate a lot plasticity. It also allows for calcium |
|
| 44:18 | through post synaptic aly it's important for because it detects both pre synaptic and |
|
| 44:24 | synaptic activity. It places it in perfect position of you know response post |
|
| 44:31 | response following pre synaptic and post synaptic to now reinforce what's happening inside the |
|
| 44:39 | . And so L. T. . Stands for long term potentially ation |
|
| 44:43 | long term plasticity and by changing activity empire then in the air receptors and |
|
| 44:49 | levels of activation you can make the more active and more plastic and more |
|
| 44:56 | of learning. Remember when we talked the biophysical properties of plasma membrane and |
|
| 45:02 | said it's a fluid mosaic model it rearranges and you have even trans membrane |
|
| 45:08 | that can move through this fluid uh and so ample receptors in particular moved |
|
| 45:17 | fast. And some of the ample live outside synapses. They're called extra |
|
| 45:23 | . And then if there is a they can get called in and they |
|
| 45:27 | travel through the membranes in the very fashion. Micro meters within milliseconds to |
|
| 45:33 | to the destination to respond potentially to synaptic input. So there is movement |
|
| 45:40 | there is exchange of these receptors post lee there's internalization of these receptors. |
|
| 45:46 | synaptic receptors expression of new insertion of receptors is all a dynamic process. |
|
| 45:53 | also dynamic because new receptors can move the synopsis to reinforce the activity there |
|
| 46:01 | glutamate metabolic tropic signaling uh is ju coupled receptors of course. So don't |
|
| 46:09 | an M. D. A receptor G. Protein coupled receptor it's just |
|
| 46:13 | not amenable tropic receptor. It's an channel but it is blocked up by |
|
| 46:18 | and it takes time for it to activated. Now a typical activation of |
|
| 46:24 | of Madaba tropical intimate receptors is G coupled receptor activation and conversion of this |
|
| 46:32 | P. I. P. Two two different molecules and divergence of this |
|
| 46:39 | . So one molecule activates one notable glutamate receptor. It produces two molecules |
|
| 46:46 | the help of possible I PAY Or P. L. C. |
|
| 46:50 | transforms P. I. P. into I. P. Three which |
|
| 46:55 | not settle triphosphate and D. G. Which is the vessel glycerol |
|
| 47:01 | triphosphate goes into the side applies and to the I. P. Three |
|
| 47:08 | channels. And these calcium channels are on smooth and the plasmid particular. |
|
| 47:14 | So in this case activation of P. Three will cause an intracellular |
|
| 47:20 | release and once again calcium will act a secondary messenger in many instances inside |
|
| 47:28 | cells the membrane associated D. G. Can interact with another chinese |
|
| 47:36 | , chinese. See that is shown And so penises again are going to |
|
| 47:42 | the p. 0. 4 They're going to cost for a late |
|
| 47:47 | possibilities. So you can either appeal a group By kindness is so you |
|
| 47:54 | take the T. 04 group from with pasta cases. Uh huh. |
|
| 48:01 | . Now where are we Gaba? we finished glutamate and we're gonna review |
|
| 48:12 | more slide that talks about glutamate and interactions. We're gonna talk about Gaba |
|
| 48:19 | this is Gaba a. Gaba Is I wanna tropic receptor channel. |
|
| 48:25 | if glutamate is responsible for E. . S. P. S. |
|
| 48:30 | synaptic deep polarization, excited personality Gaba is responsible for I. |
|
| 48:36 | S. P. S. For inhibitory post synaptic potentials. This is |
|
| 48:40 | gather receptor. Gaba is a molecule molecule will bind to these receptors when |
|
| 48:46 | bound to these receptors is going to influx of chloride. Okay and when |
|
| 48:51 | is influx of chloride. Yeah this of chloride chloride coming in it's going |
|
| 49:07 | cause and I PSP inhibitory post synaptic and that happens to influx of chloride |
|
| 49:17 | Gaba a. Mm. Now Gaba a receptor also has many different keyholes |
|
| 49:29 | different molecules to bind to the today's there's quite a few happy hours if |
|
| 49:39 | missed them on the over the over hump day, happy hours or the |
|
| 49:45 | , happy hours. Or if you alcohol, it contains ethanol and methanol |
|
| 49:52 | bind to Gaba receptors and what does do then it will cause inhibition, |
|
| 50:01 | inhibition these molecules. Ethanol is also agonist. Just like Gaba is a |
|
| 50:07 | endogenous agonist ethanol is an exogenous Gaba receptor. So you typically want |
|
| 50:15 | person is having one drink or quiet sitting around with a book or |
|
| 50:22 | But when the inhibitory gaba A receptor stimulated repeatedly with ethanol, it get |
|
| 50:32 | disinhibited. So three or four shots the bar, the person is |
|
| 50:40 | taking off clothing, having a good . There's no inhibition left. This |
|
| 50:45 | just a funny analogy, but in some of these small, if they're |
|
| 50:51 | by a certain level of ethanol will any addition, but if there's too |
|
| 50:55 | ethanol, this this this receptor is of like I don't know what to |
|
| 50:59 | with all of this ethanol and I'm going to be very efficient at handling |
|
| 51:03 | here. Other molecules that bind to a receptor important. Benzodiazepines. Um |
|
| 51:12 | hear my uh daughter listening to it's like Benzo something about Benzos is |
|
| 51:19 | wrap, right? So benzodiazepines actually . So whatever they find their way |
|
| 51:25 | in in rap music or you know different users is another story. But |
|
| 51:30 | are very common and typical anti epileptic seizure medications um very effective at stopping |
|
| 51:43 | seizures that are very strong seizures happening the brain. But the side effect |
|
| 51:50 | benzo that has opinions when they're being as medications, guess what drowsiness. |
|
| 52:02 | lot of inhibition and especially in Children have severe forms of epilepsy. Benzodiazepine |
|
| 52:11 | are pretty high and those Children act they're drunk, they are a little |
|
| 52:18 | gay is off. Walking is So this is where you have to |
|
| 52:24 | about some of the analogies between what learn in class and also the drugs |
|
| 52:28 | are out there and the effect that would see barbiturates are also sedatives |
|
| 52:35 | And also there are steroids will have binding side on on Gabba to tame |
|
| 52:40 | activity. So all of these what are they doing? They're increasing |
|
| 52:46 | and they're all anti epileptic, anti sedative like substances that that have what |
|
| 52:55 | may say, sedative effect on the inhibiting effect on neuronal activity, neuronal |
|
| 53:03 | but absolutely necessary in many cases as medications. Gaba A. Acts through |
|
| 53:13 | uh fluoride influx and Gaba B. is located nearby. Gaba B. |
|
| 53:23 | a G protein coupled receptor and Gaba . Boston ethically can open potassium channels |
|
| 53:33 | this deep learning complex very similar to tropic signaling. Right? They also |
|
| 53:40 | potassium channels. Open potassium channels, acetylcholine receptor signaling. Alright, we |
|
| 53:46 | looked earlier. So you have another here in this case. Gava |
|
| 53:52 | Gaba B receptor activation. Open potassium possum africa. You can also close |
|
| 54:02 | channels. Pre synaptic alie, what closes calcium channels? Percent optical we |
|
| 54:09 | about today we talked about endocannabinoid, G protein couple closure of present at |
|
| 54:17 | calcium channels. They have G protein closure of present at the calcium channels |
|
| 54:23 | through Gabba. So redundancy, The similar mechanisms that are used by |
|
| 54:30 | different systems and controlling the activity in cells. And this is one of |
|
| 54:36 | diagrams that I always say that if can understand this diagram, there's a |
|
| 54:42 | of notes and figure legends. There a a reference with this diagram mistaken |
|
| 54:51 | it's not from your book. It's good let's say you can erase this |
|
| 54:57 | and take notes all over this printed the page. Everything that you have |
|
| 55:02 | about Gaba and glutamate is pretty much . You know the course rampant and |
|
| 55:08 | . D. A receptor is not but you can add them here if |
|
| 55:10 | want to. So in every one my lectures I sort of have one |
|
| 55:16 | these big slides I call a summary or they may have all the subtypes |
|
| 55:22 | I say take notes and notes action diagram. Take notes and everything |
|
| 55:27 | You know what is E. Plus the equilibrium potential. Okay what |
|
| 55:31 | it? E. K. Plus 90. Same here. You can |
|
| 55:34 | the slides to take a lot of too. And let's see what's happening |
|
| 55:42 | . So we have neurons remember, can receive both inhibitory impetus, impetus |
|
| 55:50 | excitatory glutamate right on the same right, this is the same dendritic |
|
| 55:56 | here. So you have this inhibitor here coming in into the dead drive |
|
| 56:01 | inhibitor synapse louise Gaba release of Gaba activate ion A tropic Gaba A receptor |
|
| 56:14 | and will cause influx of fluoride. will activate metabolic tropic Gaba b receptor |
|
| 56:23 | which will open potassium and will cause hyper polarization. This is Gaba |
|
| 56:35 | This is Gaba B. There's certain here for the activation of this potassium |
|
| 56:45 | here through the G. Protein So that's why after Gaba is activated |
|
| 56:53 | later. Gaba B kicks in if there if that receptor is there in |
|
| 56:56 | system so you get hyper polarization posten and then more hyper polarization. This |
|
| 57:03 | the inhibitors enough. So this dendrite registered a lot of hyper polarization from |
|
| 57:11 | . It turns out that Gaba pre terminals also contain GABA B receptors. |
|
| 57:20 | if we sign optical we got the receptors can close influx of calcium. |
|
| 57:25 | this is very similar to it's also . We'll see you later to a |
|
| 57:34 | . But this is Gaba B. the inhibitory synopsis. It turns out |
|
| 57:39 | there's also got to be on the prison now this gavel when it's released |
|
| 57:47 | it can bind to these Gaba the receptors, their auto receptors because they're |
|
| 57:52 | the same cell that releases gaba and they can control their own Gaba |
|
| 57:58 | You can activate cause inhibition and then can say okay enough cause enough inhibition |
|
| 58:05 | . And then if it spills over Gambian ambience Gaba here to pre synaptic |
|
| 58:10 | support control the levels of ambition You have this glutamate ergic excitatory synapse |
|
| 58:19 | in and here you have got to hetero receptors the hetero because this is |
|
| 58:27 | glutamate terminal glutamate releasing terminal excitatory This is an M. D. |
|
| 58:33 | receptor. So activation of an D. A receptor will cause influx |
|
| 58:39 | calcium not just deep polarization and that in the excitatory post synaptic terminals can |
|
| 58:47 | with calcium cal modular Linse highnesses and kind of cases can interact with Gaba |
|
| 58:56 | receptors that are located on excitatory synapses optically that can either open potassium channels |
|
| 59:07 | eventually and essentially inhibit the excitatory So how did we get inhibition and |
|
| 59:17 | our synapse because we have inhibitor receptors . There's no inhibitory neurotransmitter here but |
|
| 59:28 | is a cascade through calcium that inhibits arson optical through the Gaba B receptors |
|
| 59:37 | through the control of potassium channels. this nearby synapse Gaba ergic synapses releasing |
|
| 59:46 | lot of Gaba this Gabba will spill and it will affect Gaba B receptors |
|
| 59:53 | are hetero receptors and it will shut excitatory neurotransmitter release. Right so it's |
|
| 60:05 | interesting how you have this inhibitor synapse and it's all inhibitor here you have |
|
| 60:12 | excitatory synapse and it has all of components of inhibition apart from Gabba and |
|
| 60:19 | can be inhibited still buy Gaba prison or through calcium signaling posson optical so |
|
| 60:29 | is it is it is pretty complex you look at this but if you |
|
| 60:34 | pass out individual components and M. . A. Calcium channel it's all |
|
| 60:40 | you know that calcium here is necessary a particular release will really learn this |
|
| 60:46 | just add action potential. That means polarization and calcium unnecessary particularly bust. |
|
| 60:54 | flora potassium Gabba a early component of . Ps delay component of my |
|
| 61:02 | That's why I say the slide is good slide to walk through. Don't |
|
| 61:06 | about the back propagating action potential But it's a good slide to walk |
|
| 61:12 | to understand the signaling from pre synaptic . Um Is there like a |
|
| 61:18 | You know there's like re uptake method or license um involved after the |
|
| 61:26 | And so is that and that occur to the spillover of Gaba? Yeah |
|
| 61:32 | and and and again like so for then what you're saying is that shouldn't |
|
| 61:36 | transporters be kicking it back in prison will be. But if if you |
|
| 61:41 | a lot of stimulation in that particular it will belong other than that you're |
|
| 61:47 | it will be cleared by the Gaba locally. But those are the instances |
|
| 61:52 | you're still over because there's a lot in condition happening in the synopsis there's |
|
| 61:56 | lot of inhibitory Gaba release. This actually some of the work that I |
|
| 62:03 | as a graduate student and it's related this. Except that what this shows |
|
| 62:09 | that quite often you will see following stimulation you will see an E. |
|
| 62:16 | . S. P. Excitatory post potential that is followed by I. |
|
| 62:22 | . S. P. S. if you're stimulating some fibers. Remember |
|
| 62:28 | doing an electrophysiology experiment. You're stimulating an electrode onto these fibers. Some |
|
| 62:35 | these fibers will be Gaba. And of these fibers will be glutamate. |
|
| 62:42 | can stimulate inhibit the excitatory. And this is what I did as a |
|
| 62:46 | student. I had a really cool where isolated the optic nerves from little |
|
| 62:54 | . And those optic nerves were connected a part of the brain called the |
|
| 62:59 | that processes visual information. And I able to stimulate the optic nerves about |
|
| 63:05 | centimeter away from where I was doing which is a huge distance for these |
|
| 63:11 | of recordings. And what I would see is I would see this very |
|
| 63:15 | E. P. S. Which was sculpted immediately by Gabba |
|
| 63:21 | Chloride. And then medical tropic gotta gotta be potassium influx. And I |
|
| 63:29 | about what happens here in this diagram Q. Colin. Is a blocker |
|
| 63:33 | Gaba. A. So if you here E. P. S. |
|
| 63:37 | . Followed by I. P. . P. Which is a normal |
|
| 63:41 | in condition to you block inhibition and happens to get this massive uncontrolled |
|
| 63:49 | So this paper talked about how inhibition and sculpts the excitation excited arpa synaptic |
|
| 63:59 | very briefly we will mention the Protein complexes. They're different. You |
|
| 64:04 | seven membrane spending off the helix is neurotransmitter binds to their separate there's no |
|
| 64:13 | but the binding of the neurotransmitter of ligand will cause a conformational change in |
|
| 64:19 | activation of this G protium complex. G protein coupled neurotransmitter receptors and we'll |
|
| 64:26 | at them even more subsequent slide sarinic lot of subtypes glutamate, medical, |
|
| 64:35 | lot of subtypes Gabby has subtypes dopamine, norepinephrine in capital, in |
|
| 64:42 | delta opioid receptors, cannabinoid CB one 2, 80 P actor dennison |
|
| 64:51 | So we'll look at it in one . But so you can see that |
|
| 64:56 | amino acids and the means and the molecules cannabinoids and they all have their |
|
| 65:04 | little tropic signaling cascades. This is gated channel. So this is one |
|
| 65:13 | the channels that we looked at. is acetylcholine Gabay, gabay, |
|
| 65:19 | glycerine, kaine eight. And they similarities. So you have five |
|
| 65:25 | In this case you have to alpha , beta gamma and each subunit has |
|
| 65:30 | trans membrane segments here and one through . And they are channels. So |
|
| 65:37 | are live in gated channels and a of fans. These two dots here |
|
| 65:41 | show that for seed alkaline you need molecules there are two binding sites for |
|
| 65:47 | receptor channel two molecules need to bind order for that channel to open |
|
| 65:52 | Okay, so neural transmitters and what we need to know for the quiz |
|
| 66:00 | for the exam everything about a single . Okay synthesis degradation agonist antagonist. |
|
| 66:11 | you should know that we lived in and beta push pull system medical |
|
| 66:16 | One of them will encourage data is to G stimulatory will encourage cyclic GMP |
|
| 66:24 | other alpha is linked to G. . So will inhibit the production of |
|
| 66:29 | GMP. Glutamate, ample an M A C A Q X M 85 |
|
| 66:35 | a P. D. You should that Gaba and Gaba B. You |
|
| 66:41 | know that for sure in the sense Gaba acts through chloride. Gaba |
|
| 66:47 | New metal, a tropic opening off channel briefly mentioned by coagulant as an |
|
| 66:55 | for Gaba A. A. P. It's interesting because we mentioned |
|
| 67:01 | denizen dennison is also an agonist for denizen type receptor 80 P. And |
|
| 67:10 | molecule combined to denison denison is an substance which is an endogenous agonist. |
|
| 67:20 | all of them are here as a for example, these are chemical |
|
| 67:26 | But a denizen is an endogenous agonist a denizen receptor antagonist, something that |
|
| 67:33 | consume almost all of us every day caffeine. So the way a denizen |
|
| 67:39 | is a denizen blocks calcium channels pre aly and blocks glutamate release. So |
|
| 67:51 | actually it is an agonist that I to explain this except that blocks the |
|
| 67:59 | is blocking the activity. So when dennison binds two identities and receptor prison |
|
| 68:14 | it's a G protein coupled receptor A and this G protein yes, wait |
|
| 68:25 | potassium channel and it is causing potassium go out. So activation of a |
|
| 68:35 | by a dentist and agonist will open channel. It will cause hyper polarization |
|
| 68:42 | control glutamate release caffeine will block this . Therefore block potassium leaving. |
|
| 68:56 | Therefore will influence the vesicular release. controls both potassium and calcium channels present |
|
| 69:09 | . I was just turning into a . Let me redraw this. Okay |
|
| 69:18 | that is more two. This is little motor jik sent out and I'm |
|
| 69:35 | talk about costume channels rather than potassium that can affect both. I'll actually |
|
| 69:42 | both here. potassium potassium opening of channels will be hyper polarization and the |
|
| 69:51 | and receptor through G protein can open channels and through G protein it can |
|
| 69:59 | calcium channels so it can dennison when is a lot of the denison it |
|
| 70:06 | basically block glutamate release. Right, that make sense? So dennison is |
|
| 70:13 | agonist. It activates this G protein G. Protein blocks influx of calcium |
|
| 70:18 | blocks glutamate release and it makes you in the evening and caffeine will actually |
|
| 70:27 | the G. Protium. It's an and will open. Will keep these |
|
| 70:34 | channels open which will then cause glutamate . So Cathy in by being an |
|
| 70:43 | of this G per diem keeps calcium open and keep splitting it released and |
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| 70:50 | why a lot of us cannot wake in the morning properly without consuming caffeine |
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| 70:56 | having that stimulatory effect on our little systems. Yes organization and caffeine preserves |
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| 71:08 | influx of calcium and will preserve more charge more D polarizing charge present optically |
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| 71:17 | as it concerns the secular release. mostly calcium that we're looking at because |
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| 71:23 | potential will be there already. So is more important and it's a common |
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| 71:28 | as you saw uh here calcium blockade After the secular release. Gaba |
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| 71:39 | A denizen will do the same Glutamate will block this a denison and |
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| 71:47 | will actually cause more calcium to come and more glutamate release and the cannabinoids |
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| 72:00 | of G protein shuts down calcium. down the secular reviews. So it's |
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| 72:06 | agonist. If it was an antagonist CB one receptor that means it would |
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| 72:12 | calcium open and keep the secular So this system that we're talking about |
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| 72:23 | transmission system. I'm not going to able to finish. It barely got |
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| 72:27 | it in an hour and 15. have to hurry up and finish it |
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| 72:30 | quickly. It's an amplifying system. transmitter can effect the release of a |
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| 72:35 | of neurotransmitters. Multiple receptors, 100 of receptors. One reception medical tropic |
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| 72:42 | can be linked to several G protein . One g burning complex can activate |
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| 72:48 | downstream molecules enzymes. One enzyme can interactions with several downstream molecules and post |
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| 72:58 | and so on. A single K. And post correlates several potassium |
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| 73:02 | . So have a lot of amplification from this neurotransmitter release and and and |
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| 73:09 | signaling through either in a tropic you iron and with measurable tropic you have |
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| 73:14 | of these amplifying intracellular cascades. That's the case where the electrical signal, |
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| 73:19 | a fraction of electrical signal gets So there is no amplification of electrical |
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| 73:24 | , just immediate engagement of large numbers neurons. Finally you have transmitter, |
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| 73:34 | have amplification and divergence. You have . One transmitter will bind to two |
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| 73:41 | subtypes three receptor subtypes one receptor supply divergent, activate three effective systems. |
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| 73:54 | can have convergence three neurotransmitters. Abc receptors abc the same effective system let's |
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| 74:03 | cyclic mp. The all convergence of same effective system. You can have |
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| 74:08 | . How do you get to affect three? You can get two. |
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| 74:14 | three of transmitter one A a one of factor three. But you can |
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| 74:20 | use a different neurotransmitter. Let's say is norepinephrine and let's say this is |
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| 74:26 | epinephrine which will bind to be and also reach a factor three. So |
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| 74:33 | is redundancy. So if you wanted still activate effective three, if you |
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| 74:37 | the whole neurotransmitter system you could still to effective three will just be a |
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| 74:42 | way of doing it. So in way have parallel streams, redundancies, |
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| 74:47 | and divergence of these secondary messenger All right, I'm gonna end here |
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| 74:54 | and uh please review all of this neuro transmission one through four. So |
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| 75:00 | prepared for the quiz and then you're be prepared well for the test which |
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| 75:03 | going to be the review for you that point. Okay, Thank you |
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| 75:07 | being here and have a good weekend . The quizzes on monday on CASA |
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| 75:15 | moniker, please sign up for your and I'll see you all next |
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