| 00:01 | today we will finish talking about the systems and we will move into starting |
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| 00:07 | talk about uh the central nervous system will follow through with time and |
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| 00:17 | Uh neurotransmitter systems as we learned, several components. They need to have |
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| 00:23 | enzymes that have to be stored in vesicles, most of them. The |
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| 00:30 | neurotransmitters such as amino acid transmitters and means baptizes you know, stored in |
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| 00:36 | dance for festivals. And then some neurotransmitter systems that we've discussed such as |
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| 00:42 | gases or the end of cannabinoids are even stored in the vestibules at |
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| 00:48 | And their little soluble and they also in the retrograde fashion. And so |
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| 00:55 | these neurotransmitters are released they will bind their post synaptic receptors. So we |
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| 01:00 | that there are ways in which you study different aspects of neurotransmitter systems. |
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| 01:06 | you're trying to identify an enzyme is for synthesizing given molecule or you're trying |
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| 01:14 | tag a neurotransmitter receptor. He can immuno history chemistry, you can use |
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| 01:20 | situ hybridization, you can use neurotransmitter uh synaptic mimic re you can also |
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| 01:31 | the caged on caging of cage neurotransmitters other chemicals using uh laser microscopy. |
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| 01:44 | we also reviewed last lecture that glutamate from blue to me and this is |
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| 01:50 | cycle that we reviewed uh glutamate uh glutamate is monitored by glia one enzymatic |
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| 02:02 | away from glutamate is a major inhibitor gaba. So all of that inhibit |
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| 02:09 | into neurons that release Gabba will stain for God enzyme. Uh the car |
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| 02:18 | illicit will stand for a single Colin . You know really, really well |
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| 02:25 | we talked about serotonin, we talked cata Colombian cycles and in general pointed |
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| 02:32 | some important information about them that will review as we progress with the |
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| 02:40 | But as we know once acetylcholine is with the help of chat, it |
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| 02:47 | transported into the vesicles. It is in synoptic fluffed And passed in |
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| 02:54 | It combined 2 2 subtypes of acetylcholine when the civil Colin binds to nicotine |
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| 03:02 | or I on the tropic silicone it will cause an influx of sodium |
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| 03:09 | caused the polarization of the post synaptic when a single Colin binds to the |
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| 03:15 | . Quranic receptor, muscular receptors coupled g protein complex and activation of G |
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| 03:23 | complex will actually open through the shortcut will open up potassium channel and opening |
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| 03:32 | potassium channel well actually cause hyper polarization the south becoming more negative on the |
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| 03:41 | with potassium leaving the south. So have I on a tropic and Metropole |
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| 03:47 | signaling and these receptors can be co . There are several different types of |
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| 03:54 | nick and Mouskouri nick subtypes of nicotine and subtypes of masculinity receptors. They |
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| 04:01 | be found sometimes the different parts of cell, they can be found sometimes |
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| 04:09 | expressed close proximity to each other And we used and later we'll again look |
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| 04:16 | the example of norepinephrine uh norepinephrine through metal tropic pathways has this push pull |
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| 04:24 | you can imagine on the functional level the catatonic acetylcholine receptors are trying to |
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| 04:29 | polarizing neurons and the mosque quranic receptors trying to hyper polarized them. So |
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| 04:35 | also have opposing result. But the of the past synaptic neuron will largely |
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| 04:43 | on the dominant predominant or the only uh acetylcholine receptors as it may be |
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| 04:50 | the south. You have a All right. Yeah. Yeah. |
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| 04:58 | . Very small. Okay that's You can you can pick it up |
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| 05:15 | and that's why you wouldn't want to glutamate stan to identify inhibitory salts. |
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| 05:23 | , so and also a lot of when you're staying for excited terry. |
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| 05:28 | also you're not staining form neurotransmitter glutamate , but you're rather are standing for |
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| 05:35 | , maybe blue dermatologic testicle or you're for another enzyme uh terminus enzyme. |
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| 05:46 | So but it's very good question because uh you would focus in on God |
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| 05:52 | identify inhibit ourselves and for excited to , you would focus on other aspects |
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| 05:57 | these neurotransmitter systems and so you have be smart in choosing the strategy when |
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| 06:02 | design your experiments and the stains. mean it's the chemistry or whatever you're |
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| 06:07 | and identifying those things. So a of times in these techniques like immuno |
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| 06:14 | to demonstrate That are discussed previously will use two or 3 markers. And |
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| 06:20 | is often the case to you make sure you're looking at that specific |
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| 06:25 | and then make sure maybe you're looking specific subtype of that salt too. |
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| 06:30 | uh so once acetylcholine is in the lapse it gets broken down by some |
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| 06:36 | industries and to call in a city Colin is transported into the south synthesizing |
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| 06:43 | settle, coding and goes through the cycle. And most of the medications |
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| 06:48 | alzheimer's on the market are cyclical industries . And we discussed this in the |
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| 06:54 | of Alzheimer's pathology also affecting the colon neurons and Cuban ergic circuits. This |
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| 07:01 | the colon arctic neuro pharmacology. Nicotine an agonist for nicotine, it must |
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| 07:06 | from mascara. Nick Ferrari is an and anthropocene is an antagonist for their |
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| 07:13 | acetylcholine receptors. So there's different substances will open and close these receptors. |
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| 07:20 | shortcut pathway measurable tropic acetylcholine receptor uh is activation of this muscular tonic receptor |
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| 07:31 | of the g protein complex and opening the potassium channel potassium leaving the south |
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| 07:38 | hyper polarization inside the south. The for glutamate for the excited to |
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| 07:48 | It's very much regulated by leah and as you can see once glutamate is |
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| 07:53 | neuronal glutamate transporters will put glutamate back neurons and stuff it back into the |
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| 07:59 | to get re released again. Once glutamate is released, it also can |
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| 08:05 | taken out by glia astrocytes nearby and into goo Thomann. Scientists with with |
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| 08:13 | time and scientists into uh groups I and then glued to me in is |
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| 08:21 | into neurons and with the help of is converted and uploaded with the help |
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| 08:28 | A. T. P. As into the vesicles. So there is |
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| 08:35 | significant regulation uh glutamate and availability of you may excitation by astrocytes and that's |
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| 08:45 | we refer to it as a tripartite , chris synaptic neuron passing out ignorant |
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| 08:51 | glial cells. Lieutenant receptors are also Torrey boston optically if their eye on |
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| 08:58 | tropic but if they are memorable tropic optically they can have multiple functions. |
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| 09:05 | of them would be hyper polarizing him . We looked at this cycle and |
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| 09:12 | looking at the cycle, It's a theme that there's a lot of pharmaceutical |
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| 09:18 | and also illicit drugs of action to neurotransmitters in the synaptic cleft whether it's |
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| 09:25 | the availability. Making more by available of a molecule by blocking the degrading |
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| 09:33 | or by blocking the transport. So and cocaine will block the co transporter |
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| 09:40 | cata column means prolonging to buy availability these mood enhancing substances that have many |
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| 09:49 | features but it's really the dopamine and . Norepinephrine is the uppers the neurotransmitters |
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| 09:57 | will dictate your upstate fight or flight if you may and dopamine as we |
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| 10:04 | about and dopamine disorders in particular would linked to movement disorders such as Parkinson's |
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| 10:12 | . And so each one of these they have a different function and they |
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| 10:16 | associated with different dysfunctions. Serotonin makes happy, gives a good mood controls |
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| 10:24 | , sleep learning. And the major depressants, anti anxiety medication branded PROzac |
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| 10:32 | prevent the serotonin reality. Prolonging the of serotonin and we talked to serotonin |
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| 10:38 | about trump trip to fan the precursor if you turkey on thanksgiving, it |
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| 10:43 | a lot of tryptophan so part of relaxation following the dinner is not just |
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| 10:48 | stuffed and full but also having a of serotonin being generated in your |
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| 10:55 | So juke rodents we saw a shortcut but when we talked about a little |
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| 11:01 | and we said there's a nicotine nick this will be the polarizing and there's |
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| 11:07 | which will be hyper polarizing through In coupled receptor nicotine it is island |
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| 11:11 | tropic. And then when we look this example with norepinephrine and we said |
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| 11:17 | they also can be linked different subtypes these amine neurotransmitter receptors can be linked |
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| 11:24 | different subtypes of g protein complexes and of these do protein complexes a stimulatory |
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| 11:30 | others are inhibitory G. I. in this case if norepinephrine bonds debate |
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| 11:36 | subtype of the receptor it actually induces the production of sidewalk and Mp and |
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| 11:43 | . Finally say and kindness is in south are responsible for force for |
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| 11:49 | we're getting the appeal for group two proteins. Uh if the same molecule |
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| 11:58 | activates an alpha receptor alpha two which linked to the inhibitory G protein |
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| 12:04 | it will inhibit and suppress the production cyclic mp. And protein financing. |
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| 12:11 | is referred to as push pull. one system is pushing to produce side |
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| 12:15 | Mp. The other systems pulling it from from being uh from increasing cycle |
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| 12:22 | of protein timing. Say this is through metal but tropic means. So |
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| 12:27 | basically have metabolic tropic receptors. It's only that I am. The tropic |
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| 12:32 | will be d polarizing. Middle of hyper polarizing. In other words they're |
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| 12:36 | actions on the same person optic You can also have two miserable tropic |
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| 12:42 | . They're opposing action through the jew complexes in targeting the same downstream pathways |
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| 12:50 | the same secondary messenger and downstream It's like a tug of war. |
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| 12:56 | is going to win. Is there alpha? Is there more beta receptors |
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| 13:00 | stimulatory? More inhibitory. And this pretty intricately tuned within the south especially |
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| 13:06 | respect to where those channels are And with relative increases of finances and |
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| 13:15 | services. Hospitalists are the enzymes that that will defeat us four allee they |
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| 13:23 | take the pillow for a group from proteins so they regulate a lot of |
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| 13:29 | through the formulation, kindnesses and foster . Because if you force for the |
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| 13:34 | you can prolong the time that protein is open for example which could be |
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| 13:41 | if it's a calcium for example protein and now you have a lot of |
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| 13:46 | influx because you prolong this activity through secondary messenger bag please. Unlike uh |
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| 13:53 | acids neurotransmitters that we send out ubiquitously throughout CNN. So if you look |
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| 13:59 | the frontal cortex there will be a of the whole bunch of south in |
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| 14:04 | cortex and layer two and three and are five and six are going to |
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| 14:08 | a toronto. South will be expressing . You'll find parameter of south expressing |
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| 14:14 | and occipital of there will be excitatory expressing glutamate of glutamate expression in the |
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| 14:20 | cord, sensory neurons. Okay, you have blue domain everywhere. So |
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| 14:27 | isn't one nucleus in the brain. area in the brain like frontal cortex |
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| 14:32 | responsible or one nucleus. Blood. is unique to the means norepinephrine is |
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| 14:39 | in local civilians. That means that selma cell bodies off these neurons are |
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| 14:46 | in one nucleus that we call locus leaves and projections external projections out of |
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| 14:53 | nucleus then innovate very broadly diffused throughout cortex and the cerebellum and into the |
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| 15:00 | cord. So if neurons die in locust, syria, leo if you |
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| 15:08 | a knife, a surgical knife or know, accident happens and there's a |
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| 15:13 | to look with serious, there wouldn't any more norepinephrine. If you if |
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| 15:19 | stab the night here there would be off the axons and endings that produce |
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| 15:25 | but you will still have a lot it being produced and distributed throughout serotonin |
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| 15:31 | nuclei. So the purple ones will the cortex and the cerebellum the green |
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| 15:37 | will supply the spinal cord. And when you zoom in here you start |
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| 15:41 | things. In fact all of that that we discussed and in particular two |
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| 15:50 | for cider acetyl kobane uh synthesis. have magnets cellular basal forebrain nucleus. |
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| 15:59 | you'll find this little girl in here uh particular protein and ladder adore Celtic |
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| 16:07 | nuclei. That's where the acetylcholine production found. That's it. So then |
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| 16:12 | fibers the neurons will send out their that will project everywhere and on to |
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| 16:18 | neurons. And then those other neurons be co expressing or expressing alpha for |
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| 16:23 | urban africa data alpha to beta beta two subunits subclass of the |
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| 16:31 | And this neurons are susceptible so it'll in neurons are susceptible to early pathology |
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| 16:39 | Alzheimer's disease and that's a strategy. how do you prolong how do you |
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| 16:45 | for more subtle Colin? And then realize while if these neurons are dying |
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| 16:50 | not that that strategy how can we the neurons and how can we have |
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| 16:56 | better treatment for Alzheimer's disease. How should all be on your minds throughout |
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| 17:00 | course sort of a euro pharmacological approaches the future of treating very difficult diseases |
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| 17:08 | don't have cures and the cannabinoids and gaseous molecules, nitrous oxide, carbon |
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| 17:17 | will affect cells in the retrograde meaning that they will buy into their |
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| 17:21 | receptors that are located pre synaptic so and then Duncan avenue and molecules will |
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| 17:28 | because there will be a lot of synaptic either Gabor glutamate activity. So |
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| 17:34 | pre synaptic neuron is going to be polarized. A lot of this pre |
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| 17:39 | activity is going to cause a lot calcium production of under cannabinoids. They |
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| 17:43 | travel retro greatly and bind to the receptors. Wong CB one receptors located |
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| 17:50 | neurons predominantly neurons and a couple of G proteins and they will shut down |
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| 17:55 | influx of calcium through voltage gated calcium . So with this deep polarization, |
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| 18:02 | there is a lot of deep polarization the cannabinoids will do they will suppress |
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| 18:07 | either the release of gaba or the of blue domains and that's what it's |
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| 18:12 | . The polarization induced suppression of More deep polarization in the suppression of |
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| 18:18 | linda cannabinoid molecules. The two main and undermine into a junior shown here |
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| 18:24 | later in the course we'll also talk the fact that CB two receptors, |
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| 18:28 | second predominant cannabinoid receptor in the brain the body. I expect expressed on |
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| 18:34 | cells dominating Micro Glee and regulating slower such as inflammation and pro inflammatory cytokine |
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| 18:45 | . So again, if your CB receptor you're more concerned with synaptic transmission |
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| 18:51 | synoptic signal regulation excitation inhibition. If CB two you are more with leah |
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| 18:57 | you're more concerned about slower processes, , repair, healing processes, inflammation |
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| 19:07 | THC or DELTA nine in particular, nine. Tetrahydrocannabinol is a fighter |
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| 19:16 | Delta nine THC wants to CB one and by binding to CB one |
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| 19:23 | it doesn't only control the release of and gaba but also causes a euphoric |
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| 19:32 | . The higher fact and that is the brain and not through the lungs |
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| 19:38 | something like that. So and DELTA uh THC is found in Canada's |
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| 19:47 | In fact, Canada's plan produces a version of Delta nine THC called DELTA |
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| 19:54 | THC. A. Or the acidic asset of THC. And that's what |
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| 19:59 | plant synthesizes. It actually synthesizes non active, non intoxicating form of THC |
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| 20:06 | city form. Uh And then when see all over the festivals or Vape |
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| 20:14 | or gas stations DELTA eight THC, is unregulated substance. And it does |
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| 20:21 | come from plants, it actually comes unused CBD and then the CBD isolate |
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| 20:29 | some synthetic and heat manipulation. So synthetic process that converts Another phyto cannabinoids |
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| 20:38 | Delta eight which is semi synthetic And it's unregulated And it's relatively |
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| 20:45 | But it will mimic some of the properties as Delta nine to a lesser |
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| 20:52 | including the euphoria fact as well. be smart about it uh When you |
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| 20:59 | out now and you go by some the shops and festivals, you'll see |
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| 21:03 | things, it will be very knowledgeable it all. This is glue may |
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| 21:09 | with the atomic Hassidic Urbach solicits dicker lists and the guide will convert will |
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| 21:14 | the decoder box Hill. It means will take the car boxes group off |
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| 21:19 | a Citigroup and you turn it into gabba molecule which is the major inhibitor |
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| 21:27 | . Okay, the neurotransmitter pumps, and glutamate all have pumps. They |
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| 21:33 | have medical transporters cycle through the And with glutamate you will know a |
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| 21:40 | . After today's lecture we'll start talking first i on a tropical intimate neural |
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| 21:47 | . The major subtypes are AMP And M. D. A. |
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| 21:51 | kaine. It they have their own agonists, Tampa and India and |
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| 21:56 | And they also have their own respective and antagonists. So uh I mean |
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| 22:05 | acid channels, pharmacology kinetic selectivity and glutamate ampara versus an MBA receptor |
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| 22:15 | So these are ligand gated channels. when glutamate binds to these ion a |
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| 22:21 | , we're talking about Iona tropic wagon channels binding of glutamine to these channels |
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| 22:28 | cause influx right of sodium inside the and the influx of potassium outside the |
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| 22:42 | . So when glutamate binds to pasin , you'll have ample receptor shown here |
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| 22:47 | blue and an M. D. receptor shown in pink they will be |
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| 22:52 | localized parson optically and release of glutamate bind to ampara And in the air |
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| 22:59 | . And the first receptor that will is going to be ample receptor. |
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| 23:04 | as soon as amber receptor opens its channel it allows for sodium to come |
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| 23:10 | and it causes the initial deep polarization excited for possible potential. And when |
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| 23:16 | see the potassium reflux, potassium influx responsible for the hyper polarization or re |
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| 23:23 | of the plasma membrane boston optically. you can see that as opposed to |
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| 23:31 | we started with action potentials. Those were selected to voltage gated sodium channel |
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| 23:37 | educated potassium channel. Now we're looking ligand gated channels and we're seeing that |
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| 23:43 | gated channels are different subtypes and you see also that they can conduct multiple |
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| 23:53 | through their channel. They're not Just sodium it's not glutamate dependent sodium |
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| 24:00 | we're talking about for the E. . S. Piece. Now, |
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| 24:04 | mae will also buy into an D. A receptor at the same |
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| 24:08 | . But an M. D. receptor is unique in the sense that |
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| 24:13 | the hyper polarized the rusting number of and M. D. A receptor |
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| 24:18 | closed and they're blocked with magnesium. there is a magnesium block sitting right |
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| 24:25 | , not allowing despite the fact that has been bound this receptor channel is |
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| 24:31 | open. So what needs to happen the M. D. A receptor |
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| 24:35 | open is that there needs to be polarization. And where do you get |
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| 24:40 | deep polarization? You get the deep through the influx of sodium through the |
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| 24:46 | channels that are responsible for the early of the E. P. |
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| 24:50 | B. And once you have the polarization, magnesium block will be |
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| 24:55 | Magnesium will get kicked out from inside channel. And now this an |
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| 25:00 | D. A. Receptor channel will sodium and calcium ions inside, followed |
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| 25:07 | the flux of potassium ions leaving from to the outside. So the whole |
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| 25:14 | of events is glutamate is released. binds to dampen an M. |
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| 25:18 | A. Within about the same But AMP A. D polarizes first |
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| 25:23 | causes the magnesium block to be alleviated an M. D. A receptor |
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| 25:29 | by deep polarization by an M. . Receptors and re polarization by the |
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| 25:35 | of potassium through both vampire and an channels shown here. So why are |
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| 25:42 | talking about a year when we say pharmacology, they have their own agonists |
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| 25:49 | kinetics ample receptor channel will open it membrane potential. It's the first one |
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| 25:56 | open an M. D. Is slower and it means deep polarization |
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| 26:00 | it's not much of a tropic. both had a tropic channels selectivity. |
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| 26:05 | of ample channels are selected to sodium potassium and then M. D. |
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| 26:11 | . Channels all allow for influx of and that's quite significant because if you |
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| 26:16 | calcium is not only an eye on in parson optically. But pasin optically |
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| 26:23 | is not as much concerned in changing member and potential as it is concerned |
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| 26:28 | activating intracellular secondary messenger cascades and other person optically. So these two major |
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| 26:38 | and conductance as you'll see is different them. Let's talk about conductance if |
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| 26:44 | open and pick in it. And lot of times uh these glutamate receptors |
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| 26:49 | be grouped together and pick in it then M. D. A. |
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| 26:53 | a lot of students make a mistake that an M. D. |
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| 26:57 | It's a metaphor tropic receptor. It not it is not linked with jeopardy |
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| 27:01 | complex. It just has a magnesium and it's slower on opening But ample |
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| 27:07 | I made a group together because they open both immediately interesting number and potential |
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| 27:13 | the binding of glutamate. And once open will only allow for about 20 |
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| 27:18 | simmons of conductance through that channel. an MD A channel is open and |
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| 27:25 | is just deciphering of what it stands appropriate tannic acid and festival eric acid |
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| 27:31 | an NBA. Once an MD A is open and as you know it |
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| 27:35 | some time from MD. A channel open. You need deep polarization that |
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| 27:38 | conduct 50 PICO semen. So it's times conductance of ample channels. So |
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| 27:45 | can think of an NBA channel you to wake it up. You have |
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| 27:48 | wait for it to wake up when wake up an M. D. |
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| 27:51 | receptor channel. You're gonna get a of conductance and you're gonna get also |
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| 27:56 | possum optical ample receptor channel will be by C. N. Q. |
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| 28:03 | its antagonist at cmu action. This still the pharmacology and some of |
|
| 28:08 | especially in the upper undergraduate courses or graduate courses. You may be reading |
|
| 28:14 | of the literature articles actually typically in course show you how I like to |
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| 28:21 | for some of the articles from Club . But as a reminder don't forget |
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| 28:25 | you can log on to U. . Libraries using your Kruger net |
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| 28:29 | D. And you can browse so things for free. Pub med is |
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| 28:36 | major engine for searching for medical and articles. You can also find a |
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| 28:43 | of books, a lot of other that are available for. We used |
|
| 28:47 | access digitally to read digitally or to ask for a loan to be sense |
|
| 28:54 | you for some rare articles that are available right immediately through the length systems |
|
| 29:00 | have age system can find you some interesting data or literature that you're that |
|
| 29:05 | may be looking for. And uh you read this literature there's always you |
|
| 29:12 | way that you learn how to read articles. It's the same way as |
|
| 29:18 | learn how to read a map or to use an app At first it's |
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| 29:24 | cumbersome And then on the fifth time the 10th time you're using the |
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| 29:29 | you already know where to swipe how advance through it. And so it's |
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| 29:34 | the same way. So you have look at the format of things. |
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| 29:37 | a lot of times you'll see method and sometimes there is an abstract introduction |
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| 29:45 | there's methods and a lot of students up reading at methods because it's so |
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| 29:51 | the methods. And if you really dedicate your time and reading all of |
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| 29:55 | details and you're gonna see names like feei PV or 85 seeing Quebec's and |
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| 30:00 | are ample Mckinney all of this is a separate language, you know, |
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| 30:06 | don't let it scare you. And my advice is also don't read the |
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| 30:12 | . When you're reading the paper, read the abstract, look at the |
|
| 30:18 | abstract. That's a new thing that's out in a lot of literature. |
|
| 30:22 | a graphical abstract basically. Just give a just in one figure of all |
|
| 30:27 | your findings, but you know, visual information. So, you |
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| 30:32 | the cat did this and the brain this and this is a molecule. |
|
| 30:38 | so look at that and that gives a really good kind of an overview |
|
| 30:43 | then go actually and read through the of the material, then look at |
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| 30:49 | figures and then go back and look the methods if you're not understanding how |
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| 30:56 | figures. So you can look at methods and you'll see that if you |
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| 30:59 | know it's the chemistry was using this immuno chemistries and methods. Whole cell |
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| 31:05 | crime inside out patches were used. that again? It's in the methods |
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| 31:12 | try to understand the concept for grasp the concept for us be interested |
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| 31:17 | and proceed with a thought processing where experiment, why it was done. |
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| 31:22 | the hypothesis they're trying to prove? are the tools they use? You |
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| 31:26 | get into details and then of course always a discussion. Another good thing |
|
| 31:31 | you're reading any new papers, if interested in some area and you want |
|
| 31:36 | pursue that area. The most recent from 2019 21 18. The discussion |
|
| 31:45 | for scientists to foresee to suggest things the future. And a lot of |
|
| 31:52 | if you look at the review articles original research articles, you go in |
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| 31:57 | discussion session section there might be a that is like oh my God this |
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| 32:02 | brilliant. This is exactly what I because that gives an opportunity for scientists |
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| 32:07 | fantasize based on what they see what happen in the future of what may |
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| 32:13 | to be done. And sky is limit. Obviously no longer the sky's |
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| 32:19 | limit. Now it's the universe is limit. So you have these amp |
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| 32:25 | receptors. They will be blocked by QX and India will have its own |
|
| 32:30 | . So the Iowa tropic but they their own agonists. They have their |
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| 32:34 | antagonists and M. D. A in neuroscience literature is a lot of |
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| 32:39 | referred to as coincident detector. Why it referred to as coincident detective? |
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| 32:46 | it's not enough to glutamate monster the receptor. It needs to have deep |
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| 32:54 | in order for the magnesium to exit of the NMDA receptor, not an |
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| 33:01 | . D. A receptor. If binds to it you're going to get |
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| 33:05 | of ions and deep polarization through ample receptor. If glutamate bison M. |
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| 33:12 | . A receptor that's not enough. it will detect pre synaptic activity. |
|
| 33:17 | it also needs Pazin attic deep So it coincidentally needs to know that |
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| 33:24 | is a pre synoptic stimulus glutamate and there is pasta topic deep polarization. |
|
| 33:30 | why it's a coincidence detector. It's important because then and then the Aricept |
|
| 33:38 | lot of fine stands at the crux the plasticity and plasticity rules that govern |
|
| 33:44 | plasticity and excited. There's synopsis um that it's a receptor that really truly |
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| 33:53 | the pre synaptic activity. Glutamate release with plus synoptic deep polarization it's responsible |
|
| 34:01 | the late portion of the PSP and look for individual current dynamics and voltage |
|
| 34:07 | in the next slide or two once open. The other interesting thing about |
|
| 34:15 | NMDA receptor is apart from glutamate Remember glycerine. Wait a second you |
|
| 34:23 | us listen is in spinal cord into inhibitor and a transmitter glistens serves as |
|
| 34:30 | co factor NMDA receptors. That means for this NMDA receptor to be really |
|
| 34:36 | very highly functional and open and closing efficiently, listening needs to be present |
|
| 34:42 | the synapse the co factor. So it binds to this you will have |
|
| 34:51 | of sodium and calcium inside the And of course it will allow for |
|
| 34:55 | to leave the cell. Magnesium will its own binding side inside the |
|
| 35:00 | In fact there are two binding channels binding sites for magnesium. There's also |
|
| 35:06 | zinc binding site and this is an . D. A receptor is aside |
|
| 35:11 | many different pharmacological and uh it's a for pharmacological and also target for some |
|
| 35:19 | the illicit drugs such as PCP which cause hallucinations and almost an acute |
|
| 35:28 | Uh PCP angel dust on the streets the name. And this is through |
|
| 35:35 | M. D. A receptor activation one time use of some of these |
|
| 35:40 | . Just especially synthetic hallucinogen johnson. don't know what's happening with them. |
|
| 35:47 | fact synthetic cannabinoids. Delta it is synthetic because it's derived from fighter phenomena |
|
| 35:55 | synthetic cannabinoids which are still prevalent and in the head shops, synthetic anonymous |
|
| 36:02 | be highly addictive and deadly. Synthetic can cause acute mania active schizophrenia and |
|
| 36:14 | had over two dozen people die in park from synthetic cannabinoids about three or |
|
| 36:19 | years ago. This is very different medical marijuana. This is very different |
|
| 36:25 | fighter cannabinoid THC and how it interacts the body. And so most of |
|
| 36:31 | things that are synthetic are impactful but can be long lasting effect for a |
|
| 36:40 | long time. The consequences of re your system. uh acute schizophrenia mania |
|
| 36:47 | for 2 3 weeks, three weeks it to end probably another 23 years |
|
| 36:54 | a person maybe to come back to . So medical tropic ligament receptors are |
|
| 37:01 | different from and chicken and an NBA in their length with the program a |
|
| 37:08 | of systems and we'll talk about from little bit later. Now if you |
|
| 37:13 | at this diagram, this diagram illustrates currents For an M. D. |
|
| 37:19 | receptor. And in normal physiological conditions have 1.2 million moller of magnesium on |
|
| 37:27 | outside of the south. And what that magnesium do then? Why are |
|
| 37:33 | talking about it? Because it's an . D. A receptor blocks in |
|
| 37:36 | . D. A receptor. So you have magnesium and you're recording this |
|
| 37:40 | the current traces of minus 60 using plan but minus 30 0 positive 30 |
|
| 37:47 | 60. You're recording currents through these you apply glutamate and you're recording from |
|
| 37:52 | M. D. A receptor. will see that At -60, there |
|
| 37:56 | no opening of an M. A receptor and normal magnesium concentrations. |
|
| 38:01 | starts opening at -30. The reversal or equilibrium potential whatever you want to |
|
| 38:08 | for an M. D. A is zero millibar holds. So when |
|
| 38:14 | learned in earnest equation and when we equilibrium potentials for individual ions, sodium |
|
| 38:23 | is because those channels we're conducting and were selected to those individual islands and |
|
| 38:33 | empire other receptive channels, they conduct ionic species. So it's it's interesting |
|
| 38:43 | you remember, the reversal potential for is about positive 55 Reversal potential for |
|
| 38:51 | is negative 80, Calcium is positive . And for an M. |
|
| 38:59 | A receptor that conducts all three of ions, the reversal potential is zero |
|
| 39:04 | balls. Somewhere almost in between. you were to take this is this |
|
| 39:11 | this is a reversal potential now not an individual ion channel. So what |
|
| 39:17 | this single iron but for receptor channel permissible to two or three islands At |
|
| 39:24 | 30. You can see that there's be a lot of an M. |
|
| 39:27 | . a conductance in a positive 60 well. The same experiment can be |
|
| 39:34 | and you can remove magnesium from the cellular solution. So if you have |
|
| 39:40 | magnesium, it's actually one of the that is used to induce seizures. |
|
| 39:45 | one of the experimental models for seizures epilepsy removing magnesium because guess what happens |
|
| 39:51 | you remove magnesium from extra cellular solution does not block an M. |
|
| 39:57 | A receptor anymore. So as soon there is glutamate released, even addressing |
|
| 40:02 | and potentials like minus 60 and D. A receptor is going to |
|
| 40:07 | is going to open a lot is to open for a long time and |
|
| 40:11 | going to cause these massive person optic polarization. So this is what happens |
|
| 40:18 | the zero magnesium model for seizures or is you have over activation of glutamate |
|
| 40:25 | particular an M. D. A that causes deep polarization is a lot |
|
| 40:30 | spiking abnormal synchrony and causes these epileptic and attacks in the brain that are |
|
| 40:38 | can be perceived as abnormal waves and circuits. So burning out of the |
|
| 40:46 | out of the circus when you see the sockets and stuff, that's what's |
|
| 40:51 | . There's actually if if the brain generating enough of the activity and electrical |
|
| 40:56 | and seizures, it will burn its tissue. So that's why it's very |
|
| 41:04 | to talk about these things and sockets overdrive and we need more fuses. |
|
| 41:10 | what we need. So we recall plots now we can understand all of |
|
| 41:20 | we learned with respect to action potentials the conductance is for sodium and |
|
| 41:26 | We cannot understand that and tease apart conductance is behind eh PSP. And |
|
| 41:32 | said the early component of E. . S. P. S. |
|
| 41:35 | of emperors after the late component of . P. S. P. |
|
| 41:38 | . Because in the arrest after. you can do an experiment where you're |
|
| 41:43 | a voltage climb here. This is of your knowledge to come together. |
|
| 41:46 | if you remember voltage clamp allows you clamp numbering potentially the desired value so |
|
| 41:52 | you can isolate, you can see the currents reverse. You can isolate |
|
| 41:56 | . You can see the inward outward . You can use specific blockers for |
|
| 42:01 | and outward currents. You can look that dynamic so you can climb the |
|
| 42:06 | -80 -40 and positive 20. And you see this little dash here you |
|
| 42:14 | a glutamate stimulation. So you're applying to me And at -80 million |
|
| 42:21 | You have two lines. The first line measures the early response. And |
|
| 42:27 | I already told you, you know the early component of the E. |
|
| 42:31 | . S. P. In the responses. The amp Akeem channels. |
|
| 42:35 | norman M. D. A So you can measure this early |
|
| 42:40 | So as you change the voltage from -80, you can see it by |
|
| 42:45 | much the current changed in this earlier . And you're measuring this early response |
|
| 42:50 | this first dash line here let's say 10 5 milliseconds after the stimulus |
|
| 42:59 | And you can graph it now at mm. I'm Sorry -100. You |
|
| 43:07 | about -200 PICO amperes. I re current in PICO hampers. He change |
|
| 43:17 | voltage. So minus 100. 200 -50. About 100. These triangles |
|
| 43:30 | and this linear line are the measurements you take the measurements for the early |
|
| 43:37 | . But the E p. S -80 -40 plus 20 as you walk |
|
| 43:43 | through different clamped number and potential So the early component or the anti |
|
| 43:51 | as a linear. I've plot. if you added a second measurement here |
|
| 43:58 | you added the second dash line. you said I'm going to look at |
|
| 44:03 | late component. I want to see currents are active at the slave |
|
| 44:07 | I'm going to take the measurement about milliseconds following the stimulus instead of five |
|
| 44:15 | following the stimulus is this is the line here we call it the lead |
|
| 44:20 | line. Okay And if you measure -80, This is the closed circles |
|
| 44:29 | . There's almost no current because there's no current here at minus 40. |
|
| 44:37 | measuring an increase in current here. can see at -100. There's nothing |
|
| 44:45 | -80 -60. You start seeing some at -40. Now there is almost |
|
| 44:51 | people emperors of current here. Going negative current is inward current And then |
|
| 45:00 | you go to -40 -20 and What happens at zero value? Both |
|
| 45:09 | early component and the late component. reverse at zero. So E |
|
| 45:15 | S. B reversal potential is zero balls And played reversal potential is also |
|
| 45:24 | normals N. M. D. receptor channel reversal potential is zero |
|
| 45:31 | Amfa receptor reversal potential is also zero . What is an played potential? |
|
| 45:40 | receptor reversal potential. zero morals. conducting sodium and potassium. They're very |
|
| 45:48 | of a similar channels and their conductance and therefore uh the reverse zero millet |
|
| 45:55 | . But you can see that as d polarize the plasma membrane and |
|
| 46:00 | D. A. Conductance has increased . So the slave component this this |
|
| 46:06 | slave component. The slave component as can see it as a blue component |
|
| 46:12 | . This blue component here is an . D. A. Component of |
|
| 46:16 | PSP. So ampara is the most the linear component. It opens up |
|
| 46:23 | way and an M. D. . Is a late component. And |
|
| 46:26 | have to have the allergic reaction from bikes. Can you mute yourself |
|
| 46:38 | Hello? Yeah. So the all the NMDA current will be conducting much |
|
| 46:57 | as you can see a deep polarized . In other words there is a |
|
| 47:01 | more blue a positive 20 But a . That's just the nature. I'm |
|
| 47:09 | saying that physiologically that's what happens because the cell is going to sit around |
|
| 47:13 | resting membrane potential. It's not much in the south and action potential. |
|
| 47:21 | actual potential resting. That's sort of normal operation mode. If you stuck |
|
| 47:27 | lectured into brain that's like somewhat semi , some neurons will be active and |
|
| 47:31 | not you know fire through action Now this will not but if you |
|
| 47:36 | seizures but take magnesium out all of will start firing at the same time |
|
| 47:41 | be polarizing. So these are the of the E. P. |
|
| 47:45 | P. The early component is the is the AM for the late component |
|
| 47:50 | nonlinear, is an NBA component. the last feature in this diagram is |
|
| 47:57 | A P. V. Is applied and a P. V. Is |
|
| 48:01 | antagonist or blocker for an end to separate channels. And when you apply |
|
| 48:06 | PV and you measure early currents, will be closed and open triangles. |
|
| 48:14 | is no difference for the early components the presence of a PV. Because |
|
| 48:19 | PV is a specific blocker from an . D. A receptor. In |
|
| 48:22 | you prove it with this expand mint more time but it doesn't affect A |
|
| 48:26 | . D. Does not affect um channels. But in the presence of |
|
| 48:31 | PV. If you look at the component, this entire blue component of |
|
| 48:38 | PSP would be completely gone right. this is what you see in these |
|
| 48:45 | circles here, the closed circles is M. D. A. |
|
| 48:48 | Polarizes more current, more current The open circles is in the presence |
|
| 48:54 | a PV. You're measuring the slave and you're essentially seeing a flat line |
|
| 49:00 | biology will never see pure zero flat or you won't see it for |
|
| 49:07 | So basically this experiment proves that a does not affect the early component which |
|
| 49:14 | teased out using voltage clown but it the late component which is an |
|
| 49:20 | So now you proved you have a that blocks the late component and an |
|
| 49:24 | . D. A receptor is responsible this. Blue late current in the |
|
| 49:29 | . P. S. B. so all of that information has been |
|
| 49:43 | wow. Mhm. Uh huh. talk for a minute about Tampa channels |
|
| 50:12 | gated calcium channels glutamate gated channels I'm progeny cellular location. Big |
|
| 50:22 | Not really calcium permeability in Tampa. important are the amino acid sequences extremely |
|
| 50:34 | . And this is an illustration that a single amino acid in a very |
|
| 50:41 | amino acid sequence. It's three dimensional repentance. Restructures can influence whether that |
|
| 50:49 | is going to be permissible to calcium receptors. If you add it |
|
| 50:57 | Which is glutamine. If you have . You have glutamine and you apply |
|
| 51:02 | to make you will see very strong conductance and you'll also see the calcium |
|
| 51:11 | . Uh huh. So if you in the sequence in your membrane these |
|
| 51:17 | chance membrane segments and one and two three and four. You learned about |
|
| 51:22 | memory segments as one through 1/6 of gated sodium channel season trans membrane segments |
|
| 51:28 | an empire And one and 2 and or 4 and M. two if |
|
| 51:33 | have Q. You have sodium and have calcium. If you remove |
|
| 51:41 | You replace it with argentine, you have sodium but you don't have |
|
| 51:50 | It's extremely significant. And that's why a small sequence identifying one important keyhole |
|
| 51:59 | one important aspect of that key hall be essentially necessary and sufficient to open |
|
| 52:09 | close the doors. Um So if channels have rhythm in the conduct |
|
| 52:18 | if they don't they don't conduct So some ample channels will conduct |
|
| 52:22 | Others will not. But all in channels as witnessed in previous slides will |
|
| 52:27 | permissible to calcium. Mhm. On Germany and India only early developmental |
|
| 52:37 | That is true. You know what's in developing brain? The rules are |
|
| 52:44 | . Jabba is excited three and not . And that's because of the equilibrium |
|
| 52:50 | for chloride that's in developing branch. else is happening in developing branch? |
|
| 52:55 | a lot of NMDA receptors in the and glutamate gets released but they're silent |
|
| 53:04 | . And why are they silent because don't express Emperor receptor. So the |
|
| 53:12 | in the development get only awoken by strong stimuli but very large. Deep |
|
| 53:19 | . Not the same rules as in mature and adult brands. And the |
|
| 53:25 | are called silent Synopsis because there's an and there's glutamate release. But the |
|
| 53:30 | are not responding to release glutamate because blocking the receptors blocked with magnesium. |
|
| 53:37 | then the other thing that happens during development is this receptor subunits. Remember |
|
| 53:45 | saw the receptor subunits that coming off alpha to beta maybe one gamma When |
|
| 53:51 | . D. A receptor it's NR and NR two subunits it's a little |
|
| 53:58 | uh lingo for FDA receptors and there a ratio of the center to a |
|
| 54:06 | and are to be containing an NBA will change as the brain structures in |
|
| 54:12 | circus develop ontology near the development. the trans membrane segments of units will |
|
| 54:22 | replaced with others of units will be emperor receptors and India receptors that are |
|
| 54:28 | than are to be earlier environment in ways this is all changing. You |
|
| 54:34 | a shift in the subunit composition as of the development which tells you what |
|
| 54:41 | tells you that maybe at some early receptors are permissible to certain substances like |
|
| 54:48 | or calcium and other stages their home your location and activity dependence changes with |
|
| 54:56 | activity ample moves fast and LTP. I should have mentioned that before the |
|
| 55:03 | test when we talked about plasticity I you can have potentially ation which the |
|
| 55:09 | are strengthened and that form of potentially if it is last thing is referred |
|
| 55:14 | as long term potentially ation or long plasticity but you can also weaken synopsis |
|
| 55:21 | we said you can depress the synopsis you can eliminate them. You can |
|
| 55:26 | them off, eliminate them. Get of the synopsis, you can depress |
|
| 55:30 | or weaken them. And so if weaken those synopsis of depress them you |
|
| 55:34 | have long term plasticity but its long depression in this case and it's not |
|
| 55:39 | same as mental depression and mental The synaptic activity, the first the |
|
| 55:45 | activity and both long term plasticity potentially and depression are forms of learning and |
|
| 55:54 | , cellular substrate of learning and What's interesting is in the last decade |
|
| 56:01 | so and being very cool demonstrations how receptor moves very fast and there is |
|
| 56:10 | NBA receptors and ample receptors that are outside the synopsis there called extra synaptic |
|
| 56:17 | but with certain levels of stimulus and . They can actually Russian to the |
|
| 56:24 | . They don't have to be inserted cytoplasm. They actually move from the |
|
| 56:29 | cellular extra synaptic space into the synoptic And ample receptors can move micro meters |
|
| 56:35 | milliseconds so they're very fast. So can reinforce the synopsis with emperor |
|
| 56:42 | If let's say there is less glutamate is coming in because you're glia is |
|
| 56:48 | up and it's holding up too much made but you need to have more |
|
| 56:52 | . Person optically. So you make person attic decision for yourself because the |
|
| 56:59 | are not, the guy is not you a glutamate. You busted. |
|
| 57:02 | because we're going to say I'm going have to put more ample receptors in |
|
| 57:05 | to get to keep receiving to be in this relationship here. So and |
|
| 57:13 | the receptor in particular is very important different forms of plasticity. And so |
|
| 57:19 | even if you read literature on plasticity learning and memory there will be a |
|
| 57:25 | section is dedicated to an M. . A dependent plasticity. Uh Another |
|
| 57:32 | of plasticity we discussed was called spiked independent decision. So an M. |
|
| 57:37 | . A receptor and glutamate signaling is involved in that. So if you |
|
| 57:42 | redolent receptors but you still induce this you may not get the same levels |
|
| 57:49 | plasticity of legitimate is not functioning Especially in M. D. A |
|
| 57:55 | . So metal tropic receptor for glue maids you can have a metal tropic |
|
| 58:02 | that's linked to a pIP to a This membrane bound and activation middle tropical |
|
| 58:13 | receptor can initiate a cascade through fossil A. C. P. |
|
| 58:19 | C. and this molecule PIP two going to be split into middle name |
|
| 58:26 | I wanted to have in college called a hospital in hospital triphosphate. I |
|
| 58:33 | that would be the coolest name. come my middle name? Was |
|
| 58:37 | Was you koobus wasn't enough. I to be you cuba's impossible burgers were |
|
| 58:44 | expect me of that but I. . Three in the hospital triphosphate |
|
| 58:48 | Cool it has its own I. . Three receptor on the calcium |
|
| 58:54 | So I. P. Three will it has its own binding side on |
|
| 58:58 | calcium channels. And this calcium So located in the smooth department, |
|
| 59:03 | . Um and I'd be three binding those calcium channels will cause an intracellular |
|
| 59:08 | release. So calcium dependent calcium release other molecule that so glycerol. The |
|
| 59:15 | . G. Will be stuck close the membrane and will be regulating our |
|
| 59:21 | kinase C. P K C. can also the release of calcium can |
|
| 59:27 | influence calcium ca module and kindnesses of kindnesses. It all goes back to |
|
| 59:33 | you connoisseurs will force for a late lot of times encouraging prolonged activity of |
|
| 59:39 | channels. Hospitalizations will defense for a . Uh So it's this tug of |
|
| 59:45 | between intracellular pathways and the levels of of kindness system. Prospectuses intracellular Gaba |
|
| 59:56 | not alone. Glutamine is not alone and thats chloride in particular Gaba. |
|
| 60:04 | . So when we talk about Gabba two major subtypes of Gaba receptor |
|
| 60:09 | There's Gabba and Gabby. When we about blue teammates we talk about diana |
|
| 60:14 | ample and M. D. Kind of and model the tropic |
|
| 60:18 | When we talk about Jabba. Talk Jabba. A which is I on |
|
| 60:22 | tropic fluoride conducting receptor channel and gathered which is G protein coupled medical tropic |
|
| 60:31 | gather binding to Gabba will cause an of flora then will cause a hyper |
|
| 60:38 | and there's many substances just like And then the receptor there's many substances |
|
| 60:43 | bind to gavel receptor and there's many drugs that target in particular Gaba |
|
| 60:52 | Gaba receptor will be targeted when there's much excitation in the system and you |
|
| 60:57 | to increase inhibition. One of the targets of Gaba receptors. Benzodiazepines and |
|
| 61:05 | lot of you that are in medical are so you may hear about |
|
| 61:09 | So and so is taking benzos taking . So benzodiazepines are quite common anti |
|
| 61:17 | medications but they are also used for different diseases and symptoms. Barbiturates which |
|
| 61:23 | sedatives essentially will also bind to gather channel. There are steroids will activate |
|
| 61:31 | receptors and so will ethanol or Uh So when ethanol balance to Gaba |
|
| 61:41 | , it's like at first it causes But then after two drinks you have |
|
| 61:51 | and you start dancing on the table a few drinks. And that's because |
|
| 61:56 | little bit of ethanol will increase inhibition sedate a person. But a lot |
|
| 62:02 | ethanol will actually this regulator desensitizes channel it's all of the inhibition is going |
|
| 62:10 | be gone. And that's when dancing the table for graduation. Right grab |
|
| 62:18 | and you can see that when Gabba to Gabba. A chloride will flocks |
|
| 62:24 | extra cellular into the intracellular space Okay, so we're chloride coming in |
|
| 62:32 | going to cause hyper polarization is going cause it PSP. Yeah Gabby is |
|
| 62:39 | g protein coupled receptor. This illustrates the G proteins are seven subunit |
|
| 62:47 | 1234567. They have the amina terminals . Extra cellular, they have a |
|
| 62:54 | boxing terminals here, cytoplasmic side. they're linked to uh one of the |
|
| 63:03 | proteins that can open potassium channel an potassium channel will cause a hyper |
|
| 63:12 | So in this case both of the . A. Is causing hyper polarization |
|
| 63:18 | the tropic in B. Is also hyper polarization with metal tropical intimated was |
|
| 63:25 | opposite effect with inhibition is the same . But it can also through another |
|
| 63:30 | protein complex. It can also block channels. You have regulation of both |
|
| 63:38 | and calcium influx through the Djiboutian Yeah, but the receptors. |
|
| 63:55 | All right, this is a fun over here. Yeah. So |
|
| 64:06 | try to understand this the whole figure written here, but let's try to |
|
| 64:12 | what's what's going on and then inhibitory excitatory synapses. And let's use this |
|
| 64:18 | is an example of how the two intricately uh interconnected in many different |
|
| 64:25 | So if you have a Gaba synapse , it's an inhibitory synapse and you |
|
| 64:34 | Gaba. The Gabba can buy into idea tropic aboudi receptor channels cause influx |
|
| 64:40 | fluoride because hyper polarization and also by the plus synaptic Gabby channels open potassium |
|
| 64:49 | cause more hyper polarization. Nice inhibitory if this Gaba spills over, it |
|
| 64:57 | prison optically it has the Gaba B . And we said that that gap |
|
| 65:04 | be receptor in the previous slide you can also control calcium channel. So |
|
| 65:12 | optically if Gabby spills over and the fashion through gabby receptors present optically it |
|
| 65:19 | auto regulate its own release. Yeah daughter receptors are to regulate itself. |
|
| 65:27 | , on the side. Yeah. IBM Jabba here in the cinemas. |
|
| 65:33 | gabble bi partisan optical and God will prison ethically. And I can control |
|
| 65:38 | own gabba cycle through this record mm I can cause a lot of hyper |
|
| 65:46 | nearby. There's an excited tourists not a little party on its own releasing |
|
| 65:54 | . It's releasing glutamate. And as know is it releases glutamate. We |
|
| 65:58 | talk that will buy into the AMp India and Pakistan and India receptors that |
|
| 66:03 | cause deep polarization. It will cause of calcium. I can also cause |
|
| 66:10 | production of calcium kindness too. And what else is located here in |
|
| 66:18 | excited tourists analysis by the gavel the boston optically in the excited tourists in |
|
| 66:27 | . But why they're located he here this excited tourists in absence. We're |
|
| 66:33 | receiving gloomy but they are located nearby inhibitory synapse. And if you see |
|
| 66:40 | ambient low level of Gaba, well today, Gabby Gabby and present at |
|
| 66:45 | Gabba B. But if this Gabba level spills over. There is a |
|
| 66:50 | of Gaba. It will travel to nearby excitatory synapse post synaptic didn't explain |
|
| 67:01 | and then we'll say hey I'm gonna polarized you. So it has nothing |
|
| 67:07 | do with this glue dramaturgy transmission. has everything to do with the nearby |
|
| 67:11 | transmission but it can affect the hyper of the polarization of this process in |
|
| 67:18 | did explain. It can also spill and target Gabby receptors prison optically on |
|
| 67:25 | excited there's synopsis and close calcium and glutamate release. So in this case |
|
| 67:36 | would be closed in calcium acts very term that cannabinoids Greece and typically CB |
|
| 67:42 | receptors blocking influx of calcium so these or receptors their head or receptors because |
|
| 67:52 | Gabby receptors are located and express them to pre synaptic terminals but they are |
|
| 67:59 | from other inhibitory terminals here. So it's this is auto receptor Gabby. |
|
| 68:06 | this Gaba receptors and a receptor because an excitatory cells but boy does this |
|
| 68:12 | to have a lot of influence on whole system here. If there is |
|
| 68:17 | lot of inhibition that will actually start how much of excitation is being released |
|
| 68:23 | how much of the deep polarization is felt in the boston optic now. |
|
| 68:30 | so I highly recommend that you review and you can see the major |
|
| 68:35 | It's a nice ski nice labeling in diagram. Read this figure legend and |
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| 68:43 | all of these things in the perspective if you can understand this then you're |
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| 68:47 | me and we're making progress. The component of Gabby. The chloride component |
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| 68:54 | illustrated by some of these experiments that was crazy enough to do as a |
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| 68:59 | student. This is Gaba a component you can see if you were to |
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| 69:05 | in actually you see the E. . S. B. Excited to |
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| 69:09 | synaptic potential excitatory synapse on the cell is activated by followed by Gaba a |
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| 69:17 | influx and the late component which is which is potassium E flux. Okay |
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| 69:28 | this is the Gabba and the Gabba component. Don't confuse it. When |
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| 69:33 | talked about glutamate we said the early is amper I am a tropic. |
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| 69:38 | component is an M. D. . I am a tropic also. |
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| 69:43 | here the early component is the A tropic cab followed by memorable tropic |
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| 69:49 | be both working in the same direction as far as drawing the member and |
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| 69:54 | further away from the threshold or hyper the cells. Did these really cool |
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| 70:02 | . There's a blocker for Gaba a by curriculum and this is what happens |
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| 70:08 | you apply the blocker. This is the blocker. Trace number one And |
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| 70:15 | apply a blocker for Gabba. Hey is trace number two. So this |
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| 70:21 | is completely kept in shocked by the synopsis by Gaba in particular and if |
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| 70:27 | alleviate Gabba. Hey boom you get massive response. Mm And I won't |
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| 70:34 | into details of the hydroxy sacrifice which the manipulation of Gabby receptors in this |
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| 70:40 | . This is the g protein receptors you're seeing the seven trans membrane structures |
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| 70:47 | protein complex here and your transmitters binding it. There's very interesting neurotransmitter receptors |
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| 70:55 | are G protein couple settle cloning. can see mascara nick and you have |
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| 71:02 | masculine Except as this is not the membrane segments. This is masculine except |
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| 71:07 | one must clinic 234 would've made metal is noted. One through eight is |
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| 71:13 | one through 14 by now. There's 14 subtypes that would be receptive will |
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| 71:19 | subtypes serotonin. As you can serotonin doesn't have an island of tropic |
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| 71:24 | channel. They're all G protein coupled . Do you want the to norepinephrine |
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| 71:31 | one alpha two beta one. Data data three. And careful in okay |
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| 71:40 | , CB one CB 2 receptors 80 which has its own a denizen receptors |
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| 71:48 | one and A two A and also two Y T two X receptors to |
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| 71:53 | finds and these are all G protein systems. All right. There's no |
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| 72:01 | a traffic signal in here. This a structure of transmitter gated channel which |
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| 72:09 | different. It has these four trans segments and typically has five subunits such |
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| 72:17 | to alpha beta gamma delta subunit. you can see that these sequences in |
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| 72:30 | expression of the amino acids will essentially what kind of a receptor channel or |
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| 72:38 | subtype you become. And so you're pharmacology and molecular analysis as much as |
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| 72:47 | want to continue talking. I think I'm out of time today and they |
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| 72:52 | really start talking about the central nervous . So we will finish up talking |
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| 73:00 | the neuro pharmacology of these systems because want to also walk you through the |
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| 73:06 | of action of caffeine and it's just substance that everybody uses every day. |
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| 73:10 | now we actually have enough knowledge for to understand it. All right, |
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| 73:14 | well. So we'll come back review because it will stress on some of |
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| 73:18 | things that we talked about today and introduce the structure and function of the |
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| 73:25 | . So the next uh lecture, should have even email by me a |
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| 73:31 | about cuisine casa. We should be place. It's Friday, it's 10 |
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| 73:36 | online only. And I will confirm you later in the week. Thank |
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| 73:43 | very much. I will see you on Wednesday. Thank you all for |
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| 73:47 | zoom. Yeah, Yeah. |
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