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BIOL 4315 Neuroscience Mo Wed 4-5.30pm - NEURO Lecture 05 RESTING MEMBRANE POTENTIAL
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00:02 This is lecture five of neuroscience. lecture we discussed the functions of real
00:09 . We talked about the micro glial and in your class supporting electoral
00:15 You have the videos or the links the videos that show the micro glial
00:20 are the most mobile units. There's , they're involved in neuronal repair following
00:27 and they moved through neuronal tissue. as there is damage in the air
00:30 will first extend their processes and then physically move through the tissue into those
00:37 in order to repair the damaged And the other big function that they're
00:41 in is inflammation and regulation of pro cytokines and release of those pro inflammatory
00:50 . So release of inflammatory molecules or is just a normal reaction of the
00:56 reaction immune reaction of the body reaction an inflammation but uncontrolled release of inflammation
01:03 what you're hearing specialist. It is to covid cytokine storms or uncontrolled cytokine
01:10 is when the cytokine release in this in the brain is not being properly
01:17 by glial cells in particular by microglia other glial cells and then the body
01:23 by other cells that mediate the side time release. So a ligo dendrites
01:28 we briefly discussed and we will talk about illegal deandra sites were involved in
01:33 elimination and creation of these myelin sheets the axons and the C.
01:39 S. And we'll come back to in a second because we'll add two
01:43 disorders to talk about today as they especially to d my elimination and dysfunction
01:50 myelin in the cns or in the astra sides. We spend probably the
01:57 time talking about astrocytes and astra sides part of the tripartite synapse. And
02:04 said that both two neurons will communicate one to neuron to and and the
02:10 . It's not just neuronal communication is glia and especially astro glial cells to
02:16 this neuron transmission neuronal communication. That's we call it a try parkour three
02:21 synapse. Astro side is a part that actively involved in the birth of
02:27 . Synopsis or Synopsys genesis and regulation synaptic transmission regulation of synaptic plasticity clearance
02:35 neurotransmitters and ions is being increased locally small locations around the synopsis and redistribution
02:43 these elements throughout the astra acidic network interconnected with other astra acidic cells and
02:50 end feet of astrocytes also are part the blood brain barrier and you'll find
02:57 and feet in the capillaries on the small blood vessels in the brain micro
03:03 . And so we talked about the brain barrier and the blood brain barrier
03:09 of them to feel yourselves that have tight junctions and it's a barrier between
03:14 blood and the brain. So you of breach that barrier easily molecules that
03:20 either very small and can squeeze through thai junctions molecules that are soluble number
03:26 lipid soluble molecules, molecules that have , facilitators that can carry them across
03:33 barrier. Those are the substances that get into the brain As it relates
03:39 COVID virus anemia. And the fact Irimias, which we discussed in lecture
03:44 as a systemic Infection by COVID-19, you have high load of the virus
03:51 your blood. You have inflammation of blood brain barrier and the thai
03:57 And this anatomy, the controlling the of the molecules in a very precise
04:03 is compromised. And now you have blood brain barrier and things from the
04:09 and the viruses and the infection can into the brain. So the last
04:15 for the molecules is the extra acidic MPI processes that you see here,
04:21 brain barrier is good for not allowing to get into the brain. Blood
04:26 barrier is also as we discussed, a challenge from pharmacological perspective because most
04:33 the neuro drugs or drugs that treat conditions, epilepsy, Parkinson's disease,
04:41 migraines, they are in just a tablets or pills. It's very rare
04:47 you will see nasal sprays for drugs get directly into the brain through that
04:52 reform plate in the skull that we on day one. Most of the
04:56 are ingested and so you ingest large of drugs because it gets digested part
05:02 it gets basically wasted through the digestive . It gets broken down some of
05:07 gets broken down some of it gets by the gastric juices and then once
05:12 gets into the absorption into the system portion of that drug or molecule gets
05:18 the system which means it gets absorbed the intestinal microbial I and into the
05:27 . Now it's in your bloodstream and it has to cross the barrier to
05:33 into the brain to treat that neurological . So you're talking about a fraction
05:38 that molecule potentially getting into the grain of it is getting into the blood
05:45 then a smaller part of it is into the brain and the smaller it
05:49 the qualities that I mentioned before soluble soluble, maybe transporters of facilitators.
05:57 are the molecules that will get in be very reliable. And that's important
06:01 you think about design of neuro pharmacological or neuro drugs. Mhm. You're
06:09 pharmaceutical treatments. We talked about the cells briefly dependable cells so interestingly comprised
06:17 barrier between the brain space and uh that contains cerebrospinal fluid in the ventricles
06:25 such. And then we also talked the last type of cell and we
06:31 the movies about radial glial cells and glial cells precursors to both glia and
06:38 And during early development neurons are born a couple of very special places in
06:43 brain and then migrate throughout the brain find their final destinations. And as
06:48 do so radial glia is like their just like their ladders and little lanes
06:54 they can hang onto and gain side plasma continuity onto the radio wheel south
06:59 basically use that as a lattice Find their final destinations in different circuits
07:06 the brain. So real cells do produce action potentials. Our next 3
07:14 lectures will be dedicated to action potentials the action of the action potentials is
07:20 in neurons. Glial sauce instead produce waves and they're much smaller but they
07:28 quite significant and they're still very important the brain as far as my elimination
07:34 in the C. N. It's illegal dangerous sites and illegal dancer
07:39 will have their processes. These processes one process will form a single myelin
07:48 and so an axon can have many myelin segments along depending how long it
07:56 . And this illegal Denver aside can many processes and place each process as
08:02 individual segment and different neurons in the . That's in the cns and the
08:10 . It's the Schwann cells and Schwann are different. Each one of these
08:17 segments is an individual Schwan south with nucleus to in between the smiling
08:27 You have nodes around here. Those are important because neurons will generate the
08:35 potential here in the axon hillock or initial segment and that action potential will
08:46 or will be conducted by axons to external terminal and some axons can be
08:51 long. Think about how tall is howard and you must have some long
09:00 in the periphery. So now you long accidents. So you can have
09:06 of these marlin segments and nodes of loaded with sodium and potassium channels.
09:15 after the action potential gets generated in accident initial segment here, it will
09:20 regenerated at each noted round beer so when it arrives at the external terminal
09:26 synaptic transmission takes place. The amplitude that action potential, it's preserved exactly
09:33 same as it is at the start its initiation side here at the actual
09:39 segment. Okay, and so this astrocytes and you can see how vast
09:46 acidic processes are in these astrocytes are connected to other astrocytes. So it's
09:52 whole network of interconnected astrocytes throughout the . This is the Myelin sheets.
10:01 you took a cross section through an nerve, this is the axons off
10:07 optic nerve. And you can see is smiling essentially showing that Myelin will
10:15 this around installation sheets around the axons and this is the note of round
10:24 that we discussed where the regeneration of action potential will take place now for
10:31 Myelin compaction to happen. There are proteins or Myelin basic proteins and BPS
10:40 are involved. And if you can it's a pretty complex process because a
10:47 has to find another cell has to that it's okay for me to grab
10:53 the Saxon and start my eliminating the that gets approached with Myelin has to
11:00 , oh I recognize you as something instead of something bad, I'm gonna
11:06 you. Huh? So for this to take place and then it has
11:11 start folding and folding precisely and time the number. And so it's a
11:18 process. You have seven related Examples would be like Myelin associated
11:28 which is actually responsible for initiation of Nation and in part for cell cell
11:35 for that Violin nation too, initiate begin. So to date, we
11:45 already discussed some neurological disorders and I asked you to dedicate a page to
11:52 disease because we will come back and about Alzheimer's disease. We also talked
11:59 fragile X syndrome and Arthur's in spectrum and asked us to take notes of
12:05 . And the reason why is because also asking you in this course to
12:09 developing the understanding of how to think the disease and the basic language of
12:17 to explain what that disease is. for example, a high school student
12:24 an elderly person that is not biologically you know really has a good understanding
12:33 biology, you have to explain that to them. So how do you
12:40 ? You know, you start by , what is it, is it
12:44 it's dementia If it's dementia is What type of dementia there are actually
12:50 that occur in young men and young and young women following traumatic brain
12:55 It's called current chronic traumatic encephalopathy. all a buzz in the NFL in
13:01 contact sport where there's a possibility of . So when we talk about Alzheimer's
13:07 And then you talk about prevalence, of that disease in the 50s,
13:12 and onward. When you talk about , what's going on? We talked
13:17 Alzheimer's pathology. When you talk about , what's the symptomology? And then
13:24 we come back and talk about the , we will start talking about
13:28 So that's something that we haven't talked yet. You know, I'm sure
13:32 of you have been intrigued. And even received an email with you from
13:36 in another class. You know, can we get rid of these
13:40 You know, can we bust them ? And you know, it's
13:43 yeah, let's bust them. You , there are plaque busters. There
13:47 all sorts of things, you but that's a good way to start
13:50 about this by really learning the mechanism trying to tie that cellular mechanism can
13:56 outward clinical expression symptomology. Um, understanding of the, of the
14:03 And so we haven't talked about the aspect of the disease and neural transmission
14:08 Alzheimer's disease. And that's going to a single colon. Now, uh
14:16 spectrum disorders, fragile X, it's completely different age group. We're talking
14:21 developmental disorders, we talked about the ? it's a genetic disorder right?
14:27 there's a severe genetic deletion or gene and there is no protein that is
14:34 produced, specific protein FMR. You will not produce response. So
14:38 is the pathology, you know and we also discussed now today we're adding
14:43 more diseases. And for these we not really gonna extend the discussion beyond
14:50 . So I don't think you need make a supper page from multiple sclerosis
14:56 for shark ordinary tooth disease unless you interested in and you know and want
15:02 and maybe enrich yourself with additional reading something like that. So multiple
15:08 Them. There's a disease that is D. Myelin nation. You have
15:18 nations of axons in the C. . S. Are being dim
15:24 And you know why? Because those are thinking that Myelin as their enemy
15:31 it starts destroying and selling Myelin it an autoimmune disease And it starts occurring
15:41 middle age in the 30s as the earliest occurrences of multiple sclerosis. So
15:52 is because in part of mutations and 18 but there's also other chromosomes that
16:00 lead to a maximum of osteoporosis. need to battle leo's or it's a
16:08 . So you need to battle leo's in order to to to have multiple
16:16 . And typically when somebody tells oh a person has multiple sclerosis.
16:22 think the symptoms that you may think this tremors stars wins convulsions. So
16:34 is that happening? Because the central system axons when they lose myelin they
16:41 communicate information properly. So if the command is saying move the hand,
16:46 normal brain and normal axon says move hand and the hand moves. Then
16:52 eliminated axons are the ones that are violence. That command is not a
16:57 command. So you see move the arm and then you start moving the
17:02 arm and you're experiencing the tremor. you're experiencing rigidity And spasms as you
17:09 up. And you can imagine if have a spasm in the muscles you
17:12 just try to flex your muscle and it there for 15 minutes and see
17:17 happens. See if you can even it it's incredibly painful. So it's
17:23 from C. N. S. that. Now the outward expression of
17:28 you can have convulsions. You can have epileptic seizures when you're losing the
17:34 nation in the brain. It can affecting many different functions. It's not
17:38 about the tremors and motor functions. not a motor disorder. It can
17:43 many different areas of the brain and on which areas dominate could be more
17:49 , more intellectual memory loss issues. not just the tremors and convulsions in
17:57 lab, we want to always recreate animals. These models or or these
18:03 these disorders using animals. And so called an animal models models of the
18:09 . And so there's a Transgenic Miles where you can alter The gene and
18:17 18 and caused the myelin nations. this is normal myelin around the access
18:23 is D myelin ated. You have scant Myelin Nation here. And these
18:30 are referred to a shiver my. these transgenic animals, they replicate some
18:38 the symptomology, outward symptomology that you also see in humans. And so
18:44 very important when you do the animal . When you're reading about the animal
18:49 , it's not only that you did mutation on that chromosome, but you
18:53 to actually follow through. Is there pathology? Is there the Myelin Nation
18:57 their symptomology. And finally, can recover the loss of function? So
19:07 is something the tools to recover the of function. We didn't have until
19:11 end of the 20th century Because we understand the real chemicals, we didn't
19:19 a Siegel Cohen as neurotransmitter until We are scientists, I wasn't even
19:26 . So 1921. So our chemical and neuro pharmacology, it's all coming
19:35 the middle of 20th century and people in the sixties start talking about these
19:40 called protein channels and receptors and And there's only three people in the
19:45 that want to talk about it everybody leaves because they are thinking about something
19:49 , you know. And then it a huge, huge science. And
19:53 you have to have tools of how recover the loss of function. And
19:59 of the early studies of brain We said it's about losing the function
20:03 the injury following the surgery, neurosurgery some instances tracking the function using the
20:13 . Now, how can you rebuild function using genetics, Using neurochemistry.
20:20 in this case you can transfer effect animals with the gene. And if
20:24 transport the animals with the gene, basically are hoping that that gene and
20:28 animal that you transplant it will produce certain pro dam or will somehow rescue
20:35 of that mutation and will promote the Nation. And so on the
20:39 you have the trance pectin animal. you can see that you can partly
20:43 that Myelin Nation around the the axles have lost it. So that's multiple
20:53 . Ah you can have loss of , there's a thing that I put
20:58 and so far my lightest inflammation and my elimination. So we talked about
21:05 . The first lecture we said that you have an infection of the brain
21:10 can lead to encephalitis which is inflammation severe infections of the brain and inflammations
21:18 lead to formal itis, which is of myelin due to the infection and
21:25 severe information. Mhm. So Charcot tooth disease. In this case You
21:40 a duplication of chromosome 17 and this dan peripheral myelin protein PMP 22.
21:51 gene is duplicated and you can see due to gene duplication in this area
21:57 where the gene is duplicated. You measure the see the amount of duplicated
22:03 and you can also see too much the PMP 22 protein. Too much
22:08 mean it's going to have to much remember in biology too much can cause
22:16 lot can cause less. A lot cause more. Less can cause more
22:19 less can cause less. So in case you have too much of PMP
22:25 . But you don't have enough violence it is affecting my elimination in the
22:32 . And as the body develops and can see that this is normal Myelin
22:37 . And this is a Myelin and Marie tooth case. And as the
22:44 develops, what happens is the gait impaired and there's bodily deformities. So
22:51 most advanced countries, in urban uh people would notice uh and you
23:00 , and the regular doctor's checkups as young Children And the earlier you see
23:09 abnormalities and these deformities earlier you can the more you can be helpful to
23:16 person that has shark attack merited why why do you have the deformities
23:24 the bone is soft as you So you stretch the bone as you
23:32 . You can actually, you strain, physical strain and that will
23:36 , you know, increase the bone to and and things like that.
23:40 you stretch your body, your bones . But as a part of normal
23:46 in the periphery you have motor neurons your muscles to move your legs to
23:52 your arms and so on. And performer not not your head because everything
23:57 here up and the face is controlled other brainstem neurons and other centers the
24:04 nerves down here then. So you this issue. And if you realize
24:11 the person has some sort of a problems, you can put them in
24:16 , you can put them in the braces, hip braces, sometimes torso
24:21 and how to kind of a structure bone structure and help them preserve normal
24:29 and to avoid some of the But in some of the especially third
24:37 countries and rural areas, there are and diagnosing this early enough where there's
24:44 damage to to the bone structure and the gates. So um this is
24:51 an autoimmune disorder, but both of are the Myelin Nation disorders. One
24:56 them is in the CNS for multiple and charlotte marry tooth in the
25:04 So this concludes us talking about agree and you can always use this
25:15 Two remember all of the wheel sauce we discussed their functions, the disorders
25:24 we talked about. And don't forget radio wheel themselves, they're not in
25:30 slide but they're important for any And today we will start talking about
25:38 membrane across the resting membrane potential, membrane potential is a potential that exists
25:47 the foster lipid bi layer whereby the charge is accumulated on the side of
25:55 , inside of the south side and positive charge on the extra cellular side
26:02 the false politic by later. And if you name the outside environment of
26:08 neuron neutral, which in physics or charge in general is zero,
26:17 The ground zero. And you plucked electorate inside this neuron. Your volt
26:23 would give you a reading of -65 rolls. And so you can have
26:32 -65 Snowballs resting membrane potential. Does mean that neuron addressed? There's always
26:51 million barrels. And the answer is . Because when you see a flat
26:58 of biology, you either run away it or you try to help as
27:03 as you can. Alright, so in biology, thermal fluctuations, ph
27:12 . You made it in whatever everything all the time. And so does
27:16 rusting member in potential. And so it's sincere, find the 65 and
27:21 in some cells in some textbooks will the resting membrane potentials 1917 and someone
27:25 say -75. We'll get to the the reason why it's like that.
27:32 -65, this number of potential is to fluctuate. And if it reaches
27:38 certain member and potential level that we the threshold for action potential which is
27:44 here about -45. So that's this line is not really true representation of
27:49 rest of memory potential. But rather older or sila scope. Although they
27:54 fast, they were fast in the and 40s. They are really slow
27:59 to the modern day telescopes and computer telescopes this, once you reach this
28:06 of the threshold Value of about -45 balls, you produce the action
28:16 So, so here is the last number Yeah, Resting 100 central of
28:56 . And it's always fluctuating. So did it go up? Why does
29:00 go down and when it freezes the is my 25. Close this
29:14 This fluctuation in the number of Okay. In this case resting
29:21 It's not that it's flatline. It's because it's not producing that actually what
29:27 the creatures of special value? Will . So the reason why the membrane
29:38 polarizes is because it gets excitatory would made inputs. And the reason why
29:46 Qala rises. It gets inhuman terry a major excited, excited itself to
30:01 the action potential in that self and is amazing transmitter and it's driving a
30:08 of potential polarized levels further away and to keep down the of the
30:18 So this is the first action potential was recorded. That was actually
30:25 I don't know because the first one it was the first one published ah
30:35 they, they had to take a using Polaroid camera on top of the
30:40 still 1939, There's no emails. phone is through the operator. You
30:50 to publish a paper. How do do it? You have to type
30:54 . There's no computer control Z doesn't , cannot undo. Well why doubt
31:03 does. And then you can retire women. So, but this is
31:09 it's done. So you take a and then of course you pass it
31:12 the copies and some other photographs and you publish it. There's no
31:17 there was no computers. So then would go to the library and get
31:22 journal and look for this picture. how different times are. How many
31:28 you invented the library here. How many of you have been to
31:34 library online, you know? that's awesome. Actually more impersonal and
31:42 . Do you guys know how to pad mat or the search engines?
31:47 . Okay. Well showed some of to you maybe during the semester.
31:51 as I point to some of the articles, it's important because we live
31:55 a very strange world where you the influencers sometimes have more of a
32:02 save and scientists and and so it's that you always trace it to the
32:07 of what the source of that information so that it's a talk show host
32:13 if it's a peer reviewed scientific article in a reputable, always keep that
32:20 mind. Google is also very good two degree. So again when you're
32:26 stuff and looking and you know surfing stuff like that. Look and see
32:31 sources you are at. You not who endorses it necessarily, but
32:37 know what it is. So and it's endorsements it's usually great if it's
32:41 by third party international organizations like the Medical Association, International neuro pharmacologist society
32:50 so on. So these are the minds of the in the science
32:55 So neurons produce these action potentials and need to produce action potentials. And
33:01 lot of that happens even reflexively and we're going to start talking about reflex
33:07 but I'm also going to remind you we have already started discussing several different
33:13 of cells. And so if it you, I'm going to remind you
33:18 we have discussed today. Uh Okay. So remember we talked about
33:43 different cell subtypes. There's subtype based different things. Okay, there's different
33:51 are things that we've discussed already, going to remind you so what are
33:55 of the cells that we have already ? We looked at the hippocampal circuit
34:04 in the hippocampus, we said that are two major cells sometimes excited to
34:09 pyramidal cells and inhibit their inter neurons when we talked about the hippocampal
34:17 we said that there's a great variety inhibitor engineering's in that circuit. And
34:22 the computational complexity and variety and different that the circuit can do. It's
34:30 of the diversity of inhibitory cells, one of them speaking a slightly different
34:36 of action to town Charles and then for projection cells, production cells.
34:42 they're going to project that information into interconnected brain circuits or brain areas.
34:49 . So far out of it. . Tori you're a transmitter good on
35:03 . What else do we know about ? Polarities remember that? Multipolar.
35:11 just my symbol. You can make own. What do you think?
35:16 cell looks like about like a tournament you know a lot about it.
35:22 has an apex at the top and article done right? It has basil
35:28 riots as an axle that's projection. . Inter neuron we're gonna talk about
35:48 into neurons today. But interneuron of hippocampus. Right? So the neurons
35:57 the hippocampus inhibitory. I'm gonna transmit . Release. It's gavel. They
36:12 multipolar? Um They're local. They project long distances but rather the control
36:30 activity, local. Uh huh. talked about dorsal root ganglion cells which
36:42 also labeled as DRG and they also them this diagram here. So you
36:47 see that dorsal root ganglion cell is sensor in neuron that has its peripheral
36:55 and the muscle Stindl joints, skin for all of the Samata sensation
37:03 that information. The sangomas of the are located right outside the admit the
37:11 . Will you come and welcome? sensory neurons almost are located outside the
37:17 cord and then the central acts on spinal of this DRG cell will carry
37:25 information into the spinal cord. So dorsal root ganglia themselves are excitatory
37:37 kind of polarity to their heart. is my pseudo unipolar. We don't
37:48 talk about them as local a projection they do go into the spinal cord
37:59 they project from the periphery of the axis on the different Okay, that's
38:07 information means it's coming from the periphery muscle joints into the cns. Into
38:19 final. What's the neurotransmitter? Any ? I'm gonna guess it's bleeding.
38:37 , now en dorsal root ganglion cells contact motor neurons that are shown
38:47 The motor neurons live on the ventral of the spinal cord. So the
38:52 cell is a motor. Modern neurons to muscle. It's a neuro muscular
39:06 . Motor neuron. The neuron projects axons onto the muscle south.
39:12 back onto that extensive muscles over It's different excited for it's multi
39:36 anybody cares to guests in their I didn't hear it but I think
39:42 a little Colin. I think it's single college. Okay, we'll know
39:49 about the civil cold. I'm sorry running out of space here spinal cord
40:12 . It's inhibitor. It's my best . It releases licensing. Yeah.
40:26 it is local. Okay. You have to know the different subtypes of
40:44 inhibit the results in the african But just remember some of the things
40:49 talked about hippocampus that were important, example, the function of hippocampus.
40:54 fact that it's an archaic cortex, three layer cortex. As this diversity
40:59 inhibitors cells of the projection cells project of the hippocampus into other interconnected cortical
41:08 . Almost after all of them are this case. And you know,
41:25 . Yeah. So which brings us this uh circuit right here. Which
41:30 quite cool because when you go to doctor's office for a yearly checkup or
41:39 office, it may sit you down you'll have your leg hanging like this
41:45 then the tunnel. Hit your this here, it's called major patellar tendon
41:53 . The stimulus with a little it will hit your patella tendon right
42:00 and the sisters. The stimulus and response is going to be that your
42:04 is going to get kicked up. if you'd like to get kicked
42:08 what happens is that dorsal root ganglion communicates that information through one synapse.
42:14 what it's called. Monos synaptic one onto the motor neuron that motor neuron
42:19 releases excited to receive alkaline and causes extensive muscle this stop muscle to contract
42:27 basically kick the leg up. But you know, for every muscle there
42:33 an opposing muscle when your bicep your triceps is relaxed. When your
42:38 contract, your biceps is relaxed and . Okay, so in order for
42:44 reflex to show a regular kick off leg, you actually have to engage
42:51 synapses and in this case and engage the inhibitor into neuron in the
42:56 cord and that inhibitor interneuron will release and you say wait a second.
43:02 said that gavel is the major inhibitor . Yes, in the cortex.
43:08 politically but in the spinal cord of as the major inhibitory neurotransmitter, the
43:14 neurons will release glycerin and inhibit the neuron that projects onto the opposing
43:20 hamstring or flexor muscle. And now inhibiting the flexor muscle or relaxing the
43:28 muscle, you have a proper hotel or reflex arch reflex. Right?
43:37 that's important because you can start inferring things if you don't have a normal
43:49 such as for example, the soft doesn't work and you need to bring
43:54 a sledgehammer in order to for that to count. That's not very
44:01 But you will say why isn't Is it damaged endorsed over gangland
44:07 Maybe they're not conducting the signal, starts giving you the clue. Maybe
44:11 the parents that were damaged. So you do other tests and say,
44:16 it seems like the parents are not . Maybe it's too much uh too
44:22 of something. Or maybe you're missing . What if you're missing inhibition and
44:29 of a sudden as you're trying to this muscle, this muscle is
44:33 it's not moving, it's not You can start inferring from understanding the
44:40 the structure of that circuit, the of the south and that circuit from
44:45 very simple reflex arch, you can inferring even some of the dysfunctions actually
44:54 the level of the spinal cord reflex , because this is the arch that
44:59 get activated when you step on the . It's not going to be your
45:05 . You know, telling you stories it's okay that you stepped on the
45:08 . Don't worry about it. We'll off of it in the near
45:12 What you do is you immediately withdraw leg and it goes through this
45:16 of course. Then through ascending fibers the spinal cord, the upper centers
45:21 the brain. Get informed of what here on on on on this and
45:26 this reflex that will get informed the of the brain that are complex
45:31 Policy synaptic reflexes, there's other Stick, for example, an example
45:38 complex reflex would be the level of cns and brain stem a gag
45:46 a reaction to something nauseous, something nauseating or or nauseous stimuli otherwise.
45:59 in order for this to happen, have to produce action potentials, muscles
46:05 to contract, muscles also produce action to contract with their action potentials are
46:10 different and much longer in duration. mediated a lot of my calcium.
46:16 the neuronal action potentials are mediated by and potassium, which brings us to
46:22 fact that in order to understand the number of potential and the action
46:26 we have to start learning about the chemicals and the channels for these chemicals
46:32 are involved in the process. Some basic things we know that hydrogen and
46:40 formed water held by prevalent bombs and polar molecules such as ions and ions
46:49 cat ions. So negatively charged ions ions positively charges kati on. They
46:57 dissolve in water. I asked, that electrical charge and the form ionic
47:05 such as sodium chloride, sodium will a positive charge and plus one is
47:10 valent Chloride and -1 Small Surveillance. this valiant see if you have two
47:18 , for example, calcium two plus a dive alan it's a positive cat
47:24 has two positive charges. And so have sodium fluoride floating here in
47:29 And that's why I'm showing that because are the main ions actually that are
47:36 on the outside in the side of cellular space here. The major chemicals
47:45 dictate resting membrane potential of -65 was potential. And also the ones that
47:52 responsible for the action potential are listed at sodium potassium chloride, calcium and
48:00 you have a TPS pumps shown there is an equal distribution of charge
48:08 plasma membrane. There is a lot of the negative charge build up on
48:12 inside of the plasma membrane and each of these ions has their own respective
48:19 . These channels that we talked about respect to the action potential is called
48:25 gated channels, voltage will open and these channels. So as there is
48:30 change of the voltage change in the potential, these channels will open and
48:35 depending on their function, depending on kinetics, depending on what they're supposed
48:40 do their own. If you look is a sodium channel potassium channel chloride
48:48 calcium channel and these channels are not open. Like I said, it
48:54 be either closed or they will be and it depends on the membrane
49:00 The voltage across plasma membrane, the . T. P A. S
49:08 in to sodium molecules, brings in and takes out the potassium and it
49:16 against concentration greatly. It works against gradient because if you were to look
49:24 the concentration of the major ions, , which is listed here in Milan
49:30 has about 145 million moller on the and about 18 million moller on the
49:36 Chloride, and seven on the So sodium chloride are dominating on the
49:44 and potassium is very high on the and also the greatest disparity in the
49:51 . Everything here in the parenthesis is milli molar. But for calcium this
49:55 a micro molar. So you have micro mall or calcium on the inside
50:01 of plaza And $1.2 million, £10,000 of calcium on the outside of the
50:11 , there is not much calcium floating freely in the side of plasma neurons
50:16 other cells. Otherwise most of it bound up by calcium binding proteins,
50:21 calculators. Because especially neurons, calcium not just a devil and cat eye
50:29 it's also a secondary messenger. And can also induce calcium induced intracellular calcium
50:38 which can turn on this abnormal calcium . Too much calcium can be toxic
50:43 cells. So there's calcium toxicity or excited toxicity. It's typically related to
50:51 excited toxicity. Tune. So these let's understand how these ions pass through
50:58 channels. These channels are built out the I mean the assets that are
51:03 by the tough tight bonds. You that you have some I mean in
51:09 non essential and essential amino assets. the essential amino acids are the ones
51:17 you have to go find in the and eat and the others you have
51:22 your body. In other words there a fraction of amino acids as you
51:27 , comes from the diet and it as building blocks for the proteins.
51:34 you can string these amino assets in primary structure. You can then coil
51:41 and to this helical structure into alpha helix which is called secondary structure.
51:46 can lay them in sheets called data as a secondary structure. Each one
51:51 these alpha helix is can become a membrane segment and one of these trans
51:56 segments which is a tertiary structure Becomes part of the four trans membrane segment
52:06 . And finally that sub unit in co ordinary structure is one of the
52:11 units that will comprise typically 4567 trans subunits will have which will have trans
52:20 segments. Each one of the subunits have a certain number of segments will
52:25 the fall of top tied uh this channel here and you can have variations
52:34 these sudden units. So you can alpha alpha data, beta gamma or
52:39 say fluoride channel and then you can alpha, alpha, beta, beta
52:46 and the function of that chloride channel it has gamma or delta, will
52:50 slightly different. The kinetics of that will be slightly different. The reactivity
52:55 that channel to the changes to number potential will also vary. Channels are
53:02 always open and channels are selective. an ion enters into a channel that
53:10 will recognize it's respectable or its respective in the sense that sodium channel recognize
53:18 ion potassium will recognize potassium channels. channels are like molecular seeds and they
53:25 through these ions based on the size part and then part of the chemical
53:31 electrical interactions that happen within the channel . Single acetylcholine receptor at the neuro
53:42 junction and the muscles can conduct. stands for current like an arms log
53:50 IR can conduct 100 million ions per . That's a lot http palms on
53:57 other hand there slow and they will hundreds of ions per second. The
54:07 are selective because as you can see for example and the sodium channel have
54:13 which is surrounded by water we call waters of hydration of clouds of hydration
54:21 as the sodium is on the outside to pass through the channel, it
54:27 to this narrow part, the most part, the innermost lumen. Uh
54:33 protein channel, it gets stripped of waters and momentarily it actually gets attracted
54:42 negatively charged amino acid residue. Mhm with that. And in fact this
54:51 for palaces sodium to go into the and get hydrated on the side of
54:57 side of the plasma number. Is the case for potassium also?
55:04 that's the case for other islands. , but now think about this.
55:09 sodium is stripped off the waters by acid residues and enters inside with larger
55:14 potassium was trapped and sent back out you'll say, okay, larger down
55:20 potassium does that mean that sodium can through the potassium channel because it's larger
55:27 . It's not that simple because the will determine the size of the claws
55:34 the hydration. Huh? So I also have larger claws of
55:44 And then it's not just that it's interaction and specific structure inside the channel
55:50 will allow for sodium or potassium to preferred to enter through, you
55:55 sodium for sodium or potassium for potassium . Okay, Arms law e equals
56:08 these voltage is measured in volts and relevant scales for neurons. Melon
56:16 So when we're talking about number of , we're talking about novels current.
56:22 . Amperes in euros. It's million Micro emperors, nana, empires.
56:31 of. It depends on the application whether you're measuring activity from single cells
56:36 networks of cells and how you're doing . Resistance is in arms and neurons
56:43 very small. Only 10 micrometers in . The smaller the sell the higher
56:50 resistance and the relevant scales for neurons mega arms. Hundreds of arms.
56:57 sorry, thousands of arms. Mega for thousands of arms conductance is in
57:07 . And for neurons the relevant scale PICO. Simmons and nano.
57:13 These are the conductance is of single . Individual cells that would be measured
57:19 those scales, conductance is an inverse resistance. So when you think about
57:27 flow of the current? A very analogy that is often used to think
57:32 a host. If you have a narrow host, the pressure is going
57:38 be high in that narrow host. when when you put a tip on
57:44 let's face stronger pressure. So the is going to be high and
57:48 the resistance is going to be high that fluid to flow through a small
57:54 , it's a small neuron, so not going to be conducting a lot
58:00 it's going to have high resistance. then if you have something big that
58:05 resist spatially, it allows for a of fluid or in this case current
58:10 flow. The resistance is low, large host, large neuron and the
58:16 system higher too, since the And then if you basically rewrite arms
58:23 current is really conductance over a change voltage. Mhm. And we talked
58:36 how there is an equal distribution of and then you'll say, well,
58:41 come that sodium that there's so much sodium florida on the outside of the
58:45 ? How come it just doesn't follow diffusion laws, chemical diffusion and diffuse
58:50 plasma membrane becomes equal moller equals itself because channels are not open. The
58:57 are controlled how they're open and And there's also something else that's going
59:02 . If you just have the channels were open, you have a high
59:05 of sodium chloride. And if only all depended on the chemical diffusion,
59:11 of course you would reach the equal concentration for both ions on on each
59:17 of the membrane However, so the is going to be driving these ions
59:25 the channels. The diffusion the chemical is going to be driving these ions
59:29 the channel. But we also know it's not only a chemistry, it's
59:36 electricity. And by virtue of membrane charged in neurons having a charge.
59:45 you have an electrical charge interaction, only the chemical interaction. So this
59:51 electrochemical process. As you know, cat ions will be attracted to catatonia
59:58 is the negative end of the battery they're going to be repelled by the
60:05 and the opposite and ions will be by anna negative charge opposites attract mhm
60:15 simulates McDowell. So, separation of across the plasma membrane gives the difference
60:23 the D. M. A membrane . The charge on the inside versus
60:27 charge on the outside the trust that is 65 million balls that we talked
60:34 . The direction of net movement of charges. The current flow Reduction in
60:41 separation which is basically positive as deep because you're losing from -65. The
60:49 separation is decreasing to -55 -15 This deep polarization increase in charge separation
60:58 -75 is called hyper polarization. But we uh this is the last slide
61:06 going to review when we look at situation, we have a lot of
61:12 and let's say we have a negatively protein in the cida plaza that is
61:18 around and there are a lot of and you insert potassium channel in the
61:23 and you open that potassium channel, of the potassium is gonna follow the
61:28 gradient and we'll say okay until it's to be equal on both sides.
61:32 no, because as the positive charge going to cross and the negative charges
61:38 here because it's either kind of cross the channel for negative charges not
61:43 It's being regulated differently. And as as for example, fluoride channel positive
61:48 is now leaving and all of a all of the potassium positive charge now
61:54 on the outside of the cell, the inside of the cell more
62:02 But as you have this positive charge , it starts acting as an an
62:10 to the an ion and starts repelling potassium at the point where chemical gradient
62:20 become equal and opposite to electrical You have what is called an equilibrium
62:30 or reversal potential for each island. , in the next lecture, we
62:37 actually discuss more details about the separation charge and look into two equations,
62:45 equation for calculating equilibrium potential for ions Goldman equation for calculating resting membrane with
62:55 show. And we will then move the action potential and talk about the
63:01 of sodium and potassium ions with where equilibrium potential. And those values are
63:07 to be important to understand. Thank for being here. Thank you for
63:11 slight delay. I will stop the and maybe I'll take any chat or
63:16 questions after I do that.
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