| 00:01 | This is neuroscience Lecture five and a review that one of the important topics |
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| 00:08 | discussed last time was how do we different subtypes of neurons in the |
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| 00:14 | We use the hippocampal circuit. It's part of the brain that's important in |
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| 00:18 | formation. That's a part of the that is damaged in Alzheimer's disease. |
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| 00:23 | it is a part of the brain contains the circuit where it has excited |
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| 00:27 | parameter all cells that release excited to neurotransmitter glutamate and our projection cells that |
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| 00:37 | excited to information between. There are circuits are between interconnected regions in the |
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| 00:46 | broom. Okay, so these are for prom inal selves. If you |
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| 00:53 | to the lecture, watch the lecture time you would have understood also that |
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| 00:58 | contrast to these projection excited to a sells most of the cellular neuronal diversity |
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| 01:06 | from the different subtypes of the inhibitory neurons. We discussed the criteria by |
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| 01:12 | we classify these different inhibitor into neurons on their location cider architecture based on |
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| 01:19 | morphology and duty to external projections where axons and the synapses are forming along |
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| 01:25 | axis. Automatic and accident riddick extent these prominent sells the inhibitor into neurons |
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| 01:33 | inhibitory neurotransmitter gaba and control activity of excitatory projections also the local circuit level |
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| 01:43 | the diversity of the south stems also different markers. Itics express not just |
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| 01:48 | markets but also different channels because they different channels and markets. They also |
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| 01:54 | different electro physiological or functional responses to same or Simula stimulant from that we |
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| 02:02 | is the collective diversity of electrical behaviors neurons were different neurons in these small |
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| 02:09 | in the brain, on the local , produced very diverse activity and firing |
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| 02:16 | of properties and contribute to the complexity processing in local circuits that are then |
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| 02:23 | by prominent south at the greater extent further distances. And so when I |
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| 02:29 | showing you this diagram, I was imitating the sound of neurons. And |
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| 02:34 | because um we can convert the sound neurons, the the action potentials, |
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| 02:43 | electrical activity, these changes in electrical . We can convert into sound and |
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| 02:50 | what listening to the sound of neurons . For me when I just joined |
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| 02:55 | graduate program is what inspired me to a neurophysiologist like I was showing in |
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| 03:04 | diagrams, you can have recordings done either whole brains or in slices where |
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| 03:11 | record activity from multiple cells. These cells were subjected to the environment that |
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| 03:18 | replicating epileptic environment. And so this a slice of the brain that's alive |
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| 03:26 | the cells are alive and it's recordings are done directly from two selves. |
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| 03:32 | first it's only one cell that is . Later the self synchronized and both |
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| 03:37 | become active and they synchronize very heavily then finally one of the south stops |
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| 03:44 | again and then the saddle continues firing this whole movie as you watch |
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| 03:49 | But this is each one of the that you hear and be represents an |
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| 03:55 | potential. So listen to this pattern think about what you think about |
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| 05:12 | Okay so this is what pathological activity like neurons in general are not as |
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| 05:21 | as pictured in these traces in these . They in this case it's a |
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| 05:30 | condition that's resemblance of seizure like activity vitro. But it's important for you |
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| 05:39 | start understanding and not only understanding but through visualizing and through listening to something |
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| 05:50 | this. In particular when you listen these places represent firing off you're one |
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| 06:11 | at the same time depending where it on the time scale realize that the |
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| 06:34 | these cells are speaking, his commitment. Die lights that they're speaking |
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| 06:44 | paying for violence. One of these types of cells are doing in normal |
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| 06:55 | are how their behavior and how this also changes in in pathology. So |
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| 07:05 | is the type of the recordings that would do in the setup. Then |
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| 07:10 | talked about Glia and we talked about and the peripheral nervous system, Schwan |
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| 07:15 | the C. N. S. good undersides. We talked about impairments |
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| 07:20 | myelin dysfunctions and Charcot Marie tooth disease multiple sclerosis. So we added two |
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| 07:28 | diseases. These are mild and dysfunctions the case of um multiple sclerosis is |
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| 07:35 | autoimmune disorder that we discuss the The Myelin nation. Symptomology of multiple |
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| 07:45 | . This is shark got married tooth you have a developmental peripheral dim island |
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| 07:53 | . And it is mostly due to over expression of it is due to |
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| 08:00 | expression of PMP 22 pro dan. These are all of the main players |
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| 08:06 | we talked about except for the radio cells and the radio glial cells. |
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| 08:13 | we saw some really cool movies that have links to in the blackboard. |
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| 08:21 | talked about how radio glial cells serve hell person, the migration process for |
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| 08:29 | to find their final destination or legal sites are involved in. While the |
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| 08:33 | astra sites are involved in a lot very intricate synaptic sonata genesis, synaptic |
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| 08:45 | , glutamate and Gaba regulation in the . Uh So it's a part of |
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| 08:53 | very intricate involvement with these cells here well as a part of the blood |
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| 08:58 | barrier. Michael glial cells we talked as scavengers in response to injury and |
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| 09:04 | as well as involved in the regulation release of these inflammatory cytokines in the |
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| 09:11 | . So we reviewed a movie where saw an injury and micro glial cells |
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| 09:15 | their processes and then migrating their bodies the side of the injury. And |
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| 09:20 | for the blood brain barrier, we the year, we we first have |
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| 09:27 | understand it. Astrocytes also is the player here in patrolling and controlling what |
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| 09:36 | crossover into the brain with the help this entire barrier and that barrier and |
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| 09:44 | is formed by the tide junctions that formed between the end epithelial cells that |
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| 09:51 | essentially forming the vasculature the walls. , so this and this helium if |
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| 10:00 | functioning fine and these tie junctions are fine and these tie junctions allow for |
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| 10:08 | passage of small elements and small particles nutrients and chemicals. Because when you |
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| 10:19 | a headache, you consume a tablet that tablet goes where it goes straight |
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| 10:28 | your brain. Of course, no about it. It goes into your |
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| 10:35 | tract, goes into your digestive it gets absorbed in uh into the |
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| 10:43 | and then the blood carries that say painkiller for your headache into the into |
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| 10:52 | into the brain and into the areas the brain. Or if you're treating |
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| 10:57 | or depression, you don't inject drugs the brain. And most of the |
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| 11:04 | are delivered by tablets or capsules. another way to deliver drugs into the |
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| 11:12 | and bypass the blood brain barrier. through the nasal cavities. And that's |
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| 11:18 | how covid 19 the virus gets into brain through the nasal cavities here in |
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| 11:24 | in the base of the skull. around the dye junctions and formed the |
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| 11:32 | the walls of the vessels. You also parasites and also you have acid |
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| 11:38 | processes. So let's zoom in on . Not the best resolution but |
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| 11:45 | this is the basement membrane that is by the epithelium and you have small |
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| 11:53 | like nanoparticles or antibodies or other Drugs like L dopa, which is |
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| 12:00 | precursor for dopamine, which is uh for Parkinson's disease. So, |
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| 12:08 | what are we talking about here? talking about the fact that in normal |
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| 12:13 | this blood brain barrier plays a protective . Uh First of all is second |
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| 12:23 | all, it also presents a Two treatment from oncological treatments. |
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| 12:41 | do how many of you have heard commercials for anxiety or depression and then |
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| 12:53 | have a lot of the side effects get listed at least commercials you |
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| 13:00 | You may have a heart attack, may um kill yourself and they make |
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| 13:06 | prone to suicide. Um But more to treat depression. But then you |
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| 13:14 | have potentially constipation or just the opposite and things like that, What's happening |
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| 13:24 | to treat medications we need to get through. If you're treating a brain |
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| 13:29 | , you need to get them through into the brain through the blood brain |
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| 13:35 | . And if this blood brain barriers while and you have certain drugs and |
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| 13:41 | that are built in the correct way you can utilize ultrasound to pulse ultrasound |
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| 13:47 | deliver the drugs and very specific locations the brain because that's another problem that |
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| 13:53 | once in the blood it gets into brain. That gets into the brain |
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| 13:58 | . So these uh antibodies and these molecules like drugs will only target they |
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| 14:05 | the receptors of their respective targets only they get into the brain or |
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| 14:10 | they get into the brain, but there are receptors where there are targets |
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| 14:15 | these molecules combine to uh why do have all of the list of with |
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| 14:24 | treating depression? You're taking a drug depression but now you're having massive |
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| 14:29 | Why is that? Because this is side effect to a lot of times |
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| 14:33 | have to take a much higher concentration that active ingredient in the drug that |
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| 14:38 | consuming orally. Because a lot of will get digested and process potentially through |
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| 14:45 | digestive system and the gastric juices as . And once it gets to the |
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| 14:52 | system, only a fraction of that element was going to get into the |
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| 14:57 | once it gets into the blood, a fraction of that is going to |
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| 15:02 | through the blood brain barrier. And therefore if you have a neuro drug |
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| 15:10 | lot of times you will see that have a lot of side effects that |
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| 15:15 | associated in the periphery because a lot targets in the brain also our share |
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| 15:24 | in the periphery and also higher concentrations start affecting of drugs can start affecting |
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| 15:33 | , can start affecting liver, can overloading liver and even more so the |
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| 15:43 | side of that. So if you to get the drugs in you have |
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| 15:47 | be very careful in developing small drugs that are permissible through blood bread |
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| 15:52 | . Especially if you're talking about neuro here and drugs that you can effectively |
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| 15:58 | through the blood brain barrier to treat condition it is. Now in many |
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| 16:05 | conditions such as for example in epilepsy severe brain inflammation and other neurological |
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| 16:16 | You have a disruption of the blood barrier, you have a disruption of |
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| 16:21 | endothelial layer or you have a disruption the tight junctions and the association here |
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| 16:29 | the extra sites you have accumulation of and dying cells. You can now |
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| 16:38 | much greater separation between ostracized. So lot of molecules and even red blood |
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| 16:45 | can pass through and at the same if you have accumulation and aggregation of |
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| 16:52 | uh junk here, it now can within treatment as well in the delivery |
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| 16:59 | medicines and antibodies into the brain. So blood brain barrier is very, |
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| 17:09 | important. I'm going to see if can find something, I hope I |
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| 17:12 | communicated to you the point that it's important structure in the brain that protects |
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| 17:19 | brain at the same time, it's structure in the brain that is impeding |
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| 17:26 | delivery of drugs, especially neuro If you don't want something to cross |
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| 17:33 | the brain. You also can use to your advantage if you're developing developing |
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| 17:38 | drug that you don't want to cross blood brain barrier also impairments and blood |
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| 17:43 | barrier can cost both things that can be wiki or they can stop um |
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| 17:50 | delivery proper deliver and targeting of the into the proper locations in the |
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| 17:58 | And there is still a challenge of you get the medicines into the brain |
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| 18:02 | they are everywhere and they will buy process synaptic receptors, so to |
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| 18:06 | but they are everywhere. And to more specific than you have to use |
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| 18:12 | other techniques from outside where you can penetrate the blood brain barrier using ultrasound |
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| 18:20 | into specific regions of the brain. , here we are. Now we're |
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| 18:27 | to try to understand in their own membrane at rest. And then finally |
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| 18:33 | action potential firing. So before membrane this actual potential, it is |
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| 18:39 | what is resting membrane potential? Resting potential means that if you have a |
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| 18:45 | electorate, which is your reference electorate you say that the outside environment of |
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| 18:50 | cell is neutrally charged. zero like ground zero charge. Okay. And |
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| 18:57 | have an electrode that's connected to the to a volt meter. And you |
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| 19:04 | a micro electrode inside one of the . Like I was showing you using |
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| 19:08 | micro electrode recording techniques, then what record is this minus 65 million |
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| 19:17 | You record that this plasma membrane has negative 65 Millersville potential compared to the |
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| 19:27 | recording electrode here. So you have of negative charge on the inside side |
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| 19:34 | plasmid side of the plasma membrane, positive side on the outside. After |
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| 19:39 | brain um now discharged very quickly can through plasma membrane channels that are embedded |
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| 19:49 | plasma member and creating this very fast potential. So we'll understand that the |
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| 19:55 | in the actual potential occurs at the membrane at the cell membrane here in |
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| 20:00 | wrong number. But before we do , we're going to start understanding a |
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| 20:06 | bit why we need this fast And we're going to start also taking |
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| 20:12 | about some of the self subtypes that already mentioned. It will discuss a |
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| 20:17 | bit further. There's reflects of behavior we talked about. So when we |
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| 20:24 | about reflexive behavior that produces the action control, we need these very fast |
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| 20:31 | potentials to travel through the circuits and at the level of the spinal cord |
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| 20:38 | in order to react the nausea stimuli heat the temperature to an injury to |
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| 20:47 | that you may have stepped on. let's understand this reflexive behavior here before |
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| 20:53 | build in more into understanding how the changes. But this circuit is the |
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| 21:00 | arches the simplest kind of reflex It's when you go to the doctor's |
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| 21:05 | and neurologists office or even the general . You sit and they put apply |
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| 21:11 | little mallet. The mallet is the activates the sensory Afrin neuron here on |
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| 21:19 | patella tendon and uh this information gets up by the pseudo unit polar sensory |
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| 21:31 | root ganglion cells. Remember that they a peripheral axe on that is connected |
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| 21:37 | this case. Muscle spindle can be to the skin muscle. Spindle, |
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| 21:41 | information to peripheral acts on his character up the ganglia, the dorsal root |
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| 21:48 | , the dorsal side of the spinal and sensory neurons. So muscle located |
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| 21:54 | of the spinal cord proper. The of the sensory dorsal neurons are located |
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| 22:00 | that ganglion that bundle and neuron selma's integrated information and send that information through |
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| 22:08 | central axis on and through the dorsal of the spinal cord and to the |
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| 22:14 | cord proper in the spinal cord It can contact the motive there. |
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| 22:21 | motor neuron can get excited by the nerve. So sensory neurons will release |
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| 22:32 | terry neurotransmitter. Mhm. Excited to . Glutamate will release excited during our |
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| 22:40 | onto motor neurons. And this motor , which is a multi polar |
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| 22:46 | This is sensory neuron, the studio polar cell motor neuron is a multipolar |
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| 22:51 | motor neuron ive parent well project in case into the extensive muscle quadriceps, |
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| 23:01 | muscle releasing excitatory neurotransmitter acetylcholine onto the , causing contraction of the muscle. |
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| 23:13 | just through one synapses mono synaptic connectivity sensory neuron and this muscle spindle directly |
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| 23:22 | the motor neuron that projects into the can cause a twitch in the muscle |
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| 23:27 | the contraction. This is very powerful neuro muscular neuron motor neuron to Moscow |
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| 23:36 | . It's a very powerful, is high fidelity synapse election potential and modern |
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| 23:42 | means the twitching a muscle. So is mono synaptic connectivity. one synapse |
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| 23:49 | neuron axon onto motor neuron and that's through one synapse you have activation and |
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| 23:56 | contraction of the muscle in the For this reflex to properly move the |
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| 24:02 | and the foot up As you're being with the stimulus, you also need |
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| 24:08 | relax opposing muscle which is the hamstring the flexor muscle. And to do |
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| 24:14 | you actually now have to involve multiple or have a policy synoptic circuit to |
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| 24:22 | this motor neuron with once and apps prime and can contract this muscle. |
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| 24:29 | if this muscle is stiff it's not to be good. So you have |
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| 24:33 | activate inhibition and you activate the inhibition . You can see that sensory neuron |
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| 24:40 | ram if I they split and now acts on contacts inhibitory interneuron, south |
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| 24:46 | black and these inhibitory interneuron cells are multipolar cells of the spinal cord and |
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| 24:54 | released inhibitory neurotransmitter glazing and that inhibitory inhibits it dampens activity of these motor |
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| 25:04 | and by inhibiting the activity of these neurons. That allows the hamstring muscle |
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| 25:09 | properly relax and be stretched as the extensive muscle is contracted. Mhm. |
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| 25:19 | in reality even the knee jerk reflex be effective and to move the knee |
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| 25:27 | . To move the lower leg You can do it through one synapse |
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| 25:32 | optically. But in reality you also to activate and inhibit opposing muscle. |
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| 25:38 | have to activate the inhibitory interneuron in circuit here and relax the opposing muscle |
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| 25:47 | relaxing the opposing muscle because there's no here on this opposing muscle and the |
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| 25:55 | muscle. You have inhibited this motor . You allow for the proper contraction |
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| 26:00 | the extensive muslim. So three types neurons here pseudo unit polar dance dorsal |
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| 26:08 | ganglion sensory neurons but release excited to neurotransmitter, glutamate on the inhibitory into |
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| 26:18 | and on the motor neurons the motor are excited to and release the seal |
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| 26:23 | and cause the contractions of the muscles into neurons inhibitor and release glazing. |
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| 26:29 | this is new. I said the inhibitory neurotransmitter in the cns is |
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| 26:34 | But in the spinal cord it is and glazing will inhibit motor neurons. |
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| 26:40 | in the presence are realizing that inhibition motor neurons these muscles are going to |
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| 26:46 | properly relaxed allowing for the proper movement the knee and the proper uh mhm |
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| 26:56 | jerk or stretch tendon reflex, patella reflex. Okay so this circuit now |
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| 27:08 | thinking about what happens if a doctor an input mallet and taps and there |
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| 27:22 | no movement of the leg. Yes. What's the problem? There's |
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| 27:33 | movement of the leg and he taps the larger, stronger stimulus. Um |
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| 27:47 | small movement on the way types with really strong stimulus and there is small |
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| 27:54 | still not a full range of movement the leg. What's happening? There's |
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| 28:03 | a problem on the spine where at junction between the century and modern neurons |
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| 28:15 | gas. The dorsal root is affected it could be and it could |
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| 28:22 | So this this this could be one , right? That this this this |
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| 28:27 | is functional because you are moving the right at the synapse is functional but |
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| 28:34 | has been weakened somehow. That's one that the synapse has been weakened. |
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| 28:40 | that's one interpretation you're saying in the cord right? What if any other |
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| 28:55 | ? What if you have a fact motor neuron and motor neuron is actually |
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| 29:01 | the sensory signal but it's not functioning , not releasing their transmitter properly. |
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| 29:08 | you have to give it much stronger for to release neurotransmitter. But the |
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| 29:13 | neuron is working fine. So you , there could be other tests and |
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| 29:18 | you could do. Of course this not definitive. But this is something |
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| 29:21 | gives a neurologist and the medical doctor bit of an insight into like you |
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| 29:27 | into the spinal serpent here. What's on at the level of the spine |
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| 29:31 | . Where is the damages sensory, are the sensations? Now we'll |
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| 29:38 | Maybe that question is you still sensitive ? Itch to paint pressure to heat |
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| 29:48 | , you can resolve that. You start gaining a window of what's |
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| 29:56 | Okay, what if you take the sledgehammer here? Well, of course |
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| 30:01 | wouldn't happen. But and you still get a response then you probably know |
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| 30:08 | there's something completely wrong and you have sense of information going in uh used |
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| 30:14 | have other sensation. So you know there's something really wrong with your mother |
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| 30:19 | , right? But all of these are important because for example, if |
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| 30:25 | have an infection of the Syrian war fluid which also bathes the spinal |
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| 30:32 | And so you have infection in the basically in the cns bacterial viral infections |
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| 30:39 | as meningitis for example, it can some of the reflex of behavior. |
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| 30:46 | you will be tested not just for , patella tendon reflex but also movement |
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| 30:53 | the eyes. Or maybe touching something fingers to gain a better understanding of |
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| 31:00 | could be going on. So, if you have inflammation, if you |
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| 31:05 | infection in the spinal cord, you have already start seeing impairments of some |
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| 31:13 | these reflexive behaviors as well. but so that also explains to you |
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| 31:20 | you step off the nail first before say, oh gosh, darn it |
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| 31:25 | heard of, what was it? know? But you first step off |
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| 31:29 | it because this is a reflex that through the, through the spinal |
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| 31:33 | And so going back historically, this what Renee the cart was thinking and |
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| 31:39 | about is this biomechanical model of some that are that are reflective of some |
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| 31:45 | functions that are reflective. And then the level of the C. |
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| 31:49 | S. You can have very complex . This is really a simple reflex |
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| 31:53 | you can have very complex reflexes involved structures, polly structural policy Synaptic gagging |
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| 32:02 | for example, that you also cannot that when you react to nausea, |
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| 32:08 | uh involves several centers in the brain the brain stem um and several synapses |
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| 32:16 | be activated to produce. Also that of behavior. But of course it's |
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| 32:20 | lot more complex and more complex circuits that behavior. So the cast of |
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| 32:31 | that are important And first of building the resting number and potential and |
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| 32:36 | changing very fast during the action Water, water, water everywhere surrounded |
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| 32:44 | water um There are ions. Water course is oxygen attracts extra electrons has |
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| 32:54 | charge. Hydrogen has next positive H 20. Held by to their |
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| 33:01 | bonds. Either polar molecules ions. solving water, the ones that have |
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| 33:10 | electrical charge atoms and molecules or ions have ionic bones, sodium chloride salt |
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| 33:18 | an ionic bond difference in the number protons and electrons results in in ionic |
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| 33:27 | . Mm. This has one extra chloride negative sodium one extra proton |
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| 33:40 | It can have mono violent and a and Duyvil in calcium two plus two |
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| 33:48 | programs. Cat ions are positively charged and ions. It's different from capitol |
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| 33:55 | and Castile, positively charged I am I am is negatively charged on such |
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| 34:01 | chloride plasma membrane. If you look plasma membrane Has the four main |
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| 34:09 | The main players are the main ions are unequally distributed across part of this |
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| 34:16 | membrane dynamic structure. But that dynamic doesn't let ions do just float |
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| 34:24 | Instead, the ions are cycled through channels these pores, protein channels that |
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| 34:30 | embedded in the plasma membrane. So you look on the outside, you |
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| 34:35 | a high concentration of sodium in you here have million dollar concentration. |
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| 34:41 | $145 million dollar sodium on the outside about 18 on the inside on the |
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| 34:49 | , you also have a lot of . So sodium chloride. So it's |
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| 34:54 | very, very saline solution that you on the outside of the membrane. |
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| 35:00 | chloride under 20 million more outside. cellular cytoplasmic sightings or cellular only seven |
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| 35:06 | more potassium On the other hand, have a high concentration of potassium on |
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| 35:14 | inside of the cell. 135 million and very low. About 3, |
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| 35:19 | million moller on the outside of the . So there's cells are full of |
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| 35:25 | . The outside of the south is solution. And also you have calcium |
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| 35:32 | comparatively is low concentration on the outside mil imola compared to the other |
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| 35:41 | But what's interesting and important about calcium that the inside calcium concentration is only |
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| 35:50 | Micro Mola. So where everywhere here Mila Mola Mola Mola Mola Mola two |
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| 35:57 | Muller. This is 1.2 Mil 0.4 Microphone. This tells you that |
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| 36:05 | has the highest concentration gradient disparity across the plasma member. And that is |
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| 36:16 | because calcium controls a lot of Uh huh. And calcium when it |
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| 36:26 | inside the south, it's not only for changing the member of potential. |
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| 36:37 | fact it's not that greatly concerned with remembering potential. But instead calcium is |
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| 36:46 | important inside the South for intracellular Calcium is very important inside the cells |
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| 36:56 | um opening other costume channels for serving a secondary messenger and initiating even downstream |
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| 37:12 | cascades inside the South. So calcium is very tightly controlled and the cytoplasmic |
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| 37:18 | and the highest disparity here in concentration for calcium, the busiest molecules and |
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| 37:24 | most important ones to account for the of potential the sodium and potassium. |
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| 37:31 | in addition to these ion channels you have a T. P. |
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| 37:36 | S. Which is sodium potassium ionic which operates with the help of a |
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| 37:44 | and conversion of A. T. . The loss of one fast food |
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| 37:49 | from try fascinating to die phosphate. this drives the proton uh the the |
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| 37:57 | against the concentration gradient. So this sodium into the outside, although there's |
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| 38:06 | lot of sodium and pumps against concentration of potassium against its concentration gradient to |
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| 38:11 | inside of the cell using a teepee energy. Mhm. So let's recall |
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| 38:21 | of the basic things that we should know from basic biology that the basic |
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| 38:29 | block of these channel proteins is amino and we have a multitude of amino |
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| 38:39 | that formed peptide bonds and we have and non essential amino acids. You |
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| 38:45 | remember what those are, but you know, assets we actually have |
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| 38:52 | gain in nature. They're essential for . They come from food and diet |
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| 39:00 | there are foods that are rich in wide variety of amino acids. |
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| 39:09 | That are very important the for So we're not going to go into |
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| 39:16 | of Darlene loose seen lie seen, , lysine and then, you |
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| 39:25 | that's what do you know? It's an inhibitor and transmitter and it will |
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| 39:30 | serve a different function and the excited signaling when we talked about glutamate signaling |
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| 39:37 | NMDA receptors. So these chains of acids come together and they have the |
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| 39:46 | structure and they get joined together through bonds. So you have these polyp |
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| 39:59 | formations, you have the proteins peptide , making them into these these |
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| 40:09 | coiling them into helix is secondary tertiary beta sheets lining them as sheets, |
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| 40:15 | them into helix is each one of and can become a trance member in |
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| 40:23 | each one of these trans membrane tertiary and co ordinary structures can form |
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| 40:30 | single sub unit and several of these four or five or six in this |
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| 40:38 | five come together to form what is a protein channel. So this is |
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| 40:45 | policy peptide subunits, all of these acids joined together and then these subunits |
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| 40:52 | together and they form a channel with poor that will allow for the flux |
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| 40:58 | ions and will control the flux of across the plasma membrane. Ion channels |
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| 41:05 | selective. Mhm. So what do mean by ion channels are selective and |
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| 41:12 | channel selectivity. What we mean by is that here is an illustration, |
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| 41:22 | is an illustration of a sodium So this picture here at the |
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| 41:34 | Stop, stop this picture here at bottom that depicts ion channel sodium channel |
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| 41:42 | ion molecules and red sodium surrounded by , which is water. We also |
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| 41:49 | to it as water some hydration. so, if you zoom in on |
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| 41:53 | salad and what you'll see is that comes in. It's Aquarius solution, |
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| 41:58 | ? And its waters water water? salty water, sodium comes to sodium |
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| 42:05 | surrounded by water, some hydration. gets strength of these waters of hydration |
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| 42:11 | gets actually propelled to come inside off cytoplasmic side of the neurons And does |
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| 42:18 | very quickly. In fact as it traveling through the inner lumen of the |
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| 42:23 | , poor sodium very quickly for one interacts with a negatively charged amino acid |
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| 42:34 | here. So the innermost aluminum, is the narrowest most point, doesn't |
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| 42:40 | just strip all of the water but very quickly attracts the sodium positively |
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| 42:47 | onto its negative residue. And very interaction which propels the sodium to travel |
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| 42:56 | the channel. So these are the of the sodium molecule and the chemistry |
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| 43:04 | getting through the channel inside the cells single uh settle Colleen receptor and the |
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| 43:15 | junction can conduct. I stands for that current can conduct. Can account |
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| 43:23 | 100 million of ions per second. contrast, 80 P A. S |
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| 43:30 | ak 80 people can deliver about 100 per second. So it's slow. |
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| 43:37 | sodium channels in this case or see Colin receptor channels are fast. They |
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| 43:44 | pump a lot of ions hundreds of , millions of islands per second. |
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| 43:50 | at phs is slow. What channels their selective ionic filters? They don't |
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| 44:00 | every ion to go through. Not positively charged on can go through. |
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| 44:07 | this case potassium would also be larger potassium would get trapped and sent back |
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| 44:19 | . Okay, so it needs a opening for potassium miles to pass through |
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| 44:25 | channel. So then you will say so then if you have a large |
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| 44:31 | because potassium is larger diameter, that the smaller diameter eye on such a |
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| 44:38 | can go through potassium channels. Uh . Is that true? No, |
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| 44:49 | you review some of the things smaller ions in fact can be surrounded by |
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| 44:59 | water. Some hydration have larger attractive . So it's not just that it's |
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| 45:07 | is important at some point the size the opening of the channel. If |
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| 45:11 | pathological conditions, channel's not functioning it's open. All the channels are |
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| 45:16 | to things. But most of the these channels are normal physiological conditions are |
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| 45:21 | specific to sodium channel will be specific sodium not just based purely on size |
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| 45:26 | also in the claws of the hydration the interaction off the amino acid residues |
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| 45:33 | and the inner lumen potassium channel will specific to potassium channels. And then |
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| 45:38 | other receptor channels such as glutamate receptor or even a single Colin receptor channel |
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| 45:46 | be impermeable to sodium and potassium So these channels whether they're receptor channels |
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| 45:53 | means that the ligand gated channels or the voltage gated channels or will be |
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| 45:58 | when we discuss action potentials uh they channels can conduct ions and they are |
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| 46:12 | to these islands. Arms law Um It's okay because I are we're |
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| 46:27 | boom. Remember that Right physics. school the voltage voles and for neurons |
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| 46:39 | relevant scale is millet balls. I for current which is am pairs. |
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| 46:48 | the units that are important for neurons PICO amperes and nano amperes for current |
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| 47:00 | . These are the skills that are to neurons. Millet balls, nada |
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| 47:05 | pairs. Resistance R. Arms, high resistance Smalling than element the neurons |
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| 47:17 | 10 markets across the highest the It's measured in mega arms as the |
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| 47:23 | scale for neurons G It's conductance, is inverse of resistance one over R |
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| 47:33 | universe. Simmons. And the relevant for neurons is Ico Simmons conductance and |
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| 47:44 | Simmons through a single receptor channel for . So arms long the equals |
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| 47:51 | Refresh yourself a little bit about There is some information in the |
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| 47:57 | Uh in Appendix two for you to if you have a book to catch |
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| 48:03 | with arms law, there's a lot things that are related to Arms law |
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| 48:06 | we're going to talk to. The couple of lectures. But first let's |
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| 48:10 | now we have the separation of this across plasma number that's uneven and there |
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| 48:16 | certain forces if you have no channels the membrane, these sodium and chloride |
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| 48:22 | are not going to cross over. if you insert the ions channels in |
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| 48:29 | numbering and you have higher concentration of on one side versus diana, these |
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| 48:35 | will flow down their concentration gradient, is diffusion, it will diffuse down |
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| 48:41 | concentration gradient from high concentration areas too concentration of sodium chlorine until the concentration |
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| 48:49 | both sides of this membrane. This experimental numb brain both sides are going |
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| 48:56 | contain equal amounts of sodium and Mhm. So concentration gradient is one |
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| 49:03 | the things of concentration grade and is of the things that is going to |
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| 49:07 | ions through their specific channel sodium facility for chloride. However, as we |
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| 49:14 | , we don't have equal distribution of on the inside versus outside of |
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| 49:20 | Inside versus outside we have unequal distribution charge across plasma number and that's how |
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| 49:25 | nature made us. Uh in this , just a little bit of a |
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| 49:34 | of electric potential. So you have eye on positively charged ion is going |
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| 49:40 | be attracted to cathode, which is minus end of the pattern. And |
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| 49:46 | on negatively charged ion was going to attracted by anna, which is possibly |
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| 49:51 | battery. So what are we talking here that it's not only chemistry that |
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| 49:59 | the movement of the sirens, but also the electrical potential that opposites attract |
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| 50:05 | other and that there is an electrical minus negative 65 million molds that gets |
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| 50:12 | across plasma numbering due to uneven distribution these aisles across the plasma membrane. |
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| 50:21 | voltage or this battery because it's attractive can drive ions through channels as |
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| 50:29 | Chemistry or diffusion and electrical potential concentration electrical potential and two things that can |
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| 50:37 | ions across the membranes The separation of across the number and gives rise to |
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| 50:44 | in this city electrical potential across plasma that that the charge that you see |
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| 50:50 | on the inside versus outside equals this million balls at the level of the |
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| 50:57 | membrane addressing member and potential. The rest or VM the membrane a lot |
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| 51:05 | times equals to this separation of charge on the inside of the membrane. |
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| 51:12 | remind yourself that current flow is in direction of net movement of positive |
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| 51:19 | china ions move opposite and Catherine's positive moving with the current direction. And |
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| 51:26 | if you have a lot of separation charge, okay, if you have |
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| 51:32 | lot of separation of charge and if drive the number of potential to have |
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| 51:37 | greater separation of charge to the outside minus 75 to minus 80 you're causing |
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| 51:43 | hyper polarization. If you are reducing separations and the number of potential Of |
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| 51:51 | is getting closer to the outside potential zero to the ground -15 -45, |
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| 51:58 | causing deep polarization and it's excited to deep polarization for the south. And |
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| 52:06 | , we'll introduce and come back and about it in greater detail equilibrium financial |
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| 52:15 | some point, what you have first all is you have separation of charge |
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| 52:20 | accumulation of discharge only across plasma And that's what I said, the |
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| 52:25 | and action potentials at the level of number and the charge separations at the |
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| 52:29 | of the numbering. If you look the inside of the cytoplasmic side, |
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| 52:35 | equal neutral environment that inside core of south is neutrally charge. The membrane |
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| 52:41 | negatively charged on the inside. And you have a potassium a lot of |
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| 52:46 | concentration, you have some protein that's charged. It can diffuse across plasma |
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| 52:53 | and you have on the outside a bit of potassium so you insert this |
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| 52:59 | channel and potassium is going to flow down its concentration gradients as goes in |
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| 53:05 | to defuse into the side where there little potassium but it's not going to |
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| 53:13 | on both sides because as soon as is positive charge which is potassium |
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| 53:18 | that gets built up now on the of the cell, that positive charge |
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| 53:23 | the concentration of the potassium but the charge. That electrical force starts repelling |
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| 53:30 | more potassium from coming from high concentration end zone into low concentration gradients. |
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| 53:38 | is where you have an ionic equilibrium , abbreviated as e ionic It's a |
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| 53:46 | where diffusion national and electrical forces are in size to each other and there |
|
| 53:52 | no net ionic movement across plasma Uh huh. So now we're putting |
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| 54:02 | of these forces that electrical and the forces together that are interacting and dictating |
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| 54:10 | number of potential. So when we the following live show will start reviewing |
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| 54:16 | concepts of the driving force concepts of neurons, potential, Goldman cats potential |
|
| 54:25 | uh, and learns the equation and these different |
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