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BIOL 4315/6315 Neuroscience Tue Th - NEURO Lecture 05 Resting Membrane Potential
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00:02 this is lecture five of neuroscience. what we started discussing in the last
00:07 lectures and we will continue discussing along same themes throughout the course was different
00:14 of neurons and glia. So we about neurons or about two lectures and
00:18 said that there are different ways in we can distinguish different subtypes of
00:24 We talked about morphology, their morphological . And we'll talk about some of
00:28 cells that are on this diagram Today talk about dorsal root ganglion cells and
00:34 talk about motor neurons that are shown . Uh morphology is not enough because
00:41 of the cells look alike morphological really the same layers or the same areas
00:48 circuits of the brain but there's still different subject. And so we talked
00:54 the fact that there's other ways in we can distinguish different subtypes of cells
01:01 their projection cells which most of the cells overwhelmingly excitatory parameter cells or where
01:08 local network into neurons that are inhibitory have Gaba in cns is the major
01:20 . They also have self specific markers that's a lot of times it will
01:24 you distinguish the self subtype that looks same and that even fires these action
01:30 that we described as a dialect that the same pattern of action potentials but
01:35 can be distinguished by the substance. is neurotransmitters, neuro peptides, calcium
01:41 proteins that one cell expresses that looks same and fires the same and then
01:46 cell doesn't which also is a functional for at least the cellular signaling inside
01:51 cells which makes those two cells a subtypes of cells of neurons. So
02:00 spent quite a bit of time on circuit. And the take home message
02:05 you have to know from the circuit not necessarily the names of the markers
02:10 CD or PV. But the general that you have this three layered structure
02:16 is in the campus when we go the neocortex is going to be six
02:21 into connectivity that we'll discuss in the and outputs are gonna be more complex
02:27 we're discussing here. But in the , what happens is that in the
02:33 we have these diverse subset of inhibitory , 21 different subtypes of inhibitory cells
02:39 the local inter neurons that will dictate will control the output of these
02:46 excited ourselves. This projection excited will project out of campus to other
02:52 of the brain, communicating the information is being processed in this network and
02:58 control of that communication that goes out much is dependent on the activity of
03:04 surrounding inhibitory cells. These inhibitory cells these excitatory parameter cells will actually receive
03:12 same farmer excitatory input. So there's to be excitation. It's not like
03:18 of a sudden there's some spontaneous activity this circuit of the hippocampus is a
03:22 prominent excitatory input. It's gonna come and it's going to excite inhibitory cells
03:30 inhibit ourselves get excited. They start other cells because they start releasing gaba
03:37 the excitatory cells are excited they excite the cells. They start releasing glutamate
03:43 they start communicating that information to the networks. And so once these cells
03:50 the common input then you have a dialects in which that common input gets
03:56 in the output by the inhibitory cells finally deciding whether excitatory cells are going
04:03 pass that input projected onto the interconnected of the brain. And that's pretty
04:11 all you have to know. Three structure the rabbit hole, south livin
04:15 criminality 90% and they're boring because they have intracellular marker that distinguishes them but
04:23 else. And aspires morphology or So in this next slide and I
04:34 that cells can receive the same input they will produce a different pattern of
04:39 and that pattern of output the action . And if we look in the
04:46 regions of the brain and we actually to insert the electrodes are recording electrical
04:56 from another subset. This is a . What I described is especially these
05:03 inter neurons are going to produce complex different patterns of action potential output which
05:11 call a dialect of the south, languages action potentials but how you speak
05:16 language very much depends on different sometimes . We need that complexity because we
05:23 complex frequencies affecting our visual inputs. have sensory auditor information coming in.
05:31 frequencies Have some out of sensor information is car vibrations can be very slow
05:38 can be very fast and this is different frequencies that are still being perceived
05:42 the brain and processed by those And some of the cells will be
05:47 fast. The fastest into neurons in brain can fire 600 action potentials a
05:54 600 hertz. That's super fast. then there are some others that fire
05:59 slower patterns and just a few action are or patterns and bursting patterns
06:06 So we need that in order to all of the inputs, process all
06:13 our thoughts, intellectual abilities and things that and put out the output whatever
06:17 is hitting a ball with a tennis or speaking to the audience and so
06:28 . Then we moved on to glia we discussed different subtypes of glia and
06:34 not gonna go through all of the we discussed but throughout the last couple
06:41 lectures have pointed out certain pathologies and that we discussed. So as it
06:47 to my elimination, we talked about which is basically an inflammation following an
06:56 . But then we discussed two One is the P. N.
07:00 . Disorder Charcot Marie tooth and one a C. N. S.
07:05 disorder which is multiple sclerosis. So should review those also. And then
07:13 the end we summarized uh summarized the of the major they're not all of
07:24 sub types of glial cells will be . For example, radio glial cells
07:27 not shown here. But Michael, you remember the most mobile elements to
07:33 activated injury, inflammation are responsible for inflammatory autoimmune response in the brain.
07:43 have a little tender sides that provide in the C. N.
07:47 Have Schwann cells that provide myelin and PNS spinal nerves and then exercise.
07:54 have that are controlling here. You see by the synapses so that they're
08:00 synaptic activity but they also have their on the blood brain barrier. So
08:06 are part of one of the checkpoints substances to cross into the brain.
08:13 good thing that you can do with like this is write down all the
08:18 that you know on the slide, do do, what does Elizabeth underside
08:25 ? Has already shown what disastrous I'd what is another cell in the
08:30 M. S. You can transfer in the P. M.
08:32 So these are great for taking notes studying and reviewing And then we ended
08:38 about briefly the blood brain barrier. introduced the blood brain barrier when we
08:43 about covid 19 infections and we talked the fact that if you have a
08:48 high viral load in your blood diary and your blood and you have
08:55 Those processes like inflammation can make blood barrier loose other than that under normal
09:02 blood brain barrier as tight junctions between , the real cells so things cannot
09:07 . You have parasites and then you the astra acidic and feed here,
09:12 also has another checkpoint for things. remember that if Covid 19 crosses then
09:19 will hang on to a stew receptors those ace two receptors are expressed by
09:24 and Julia. So there's a way covid to infect neurons and glia once
09:29 inside the brain tissues and for the part, blood brain barrier serves this
09:36 protective function. So if you drink drink or something that gives you a
09:42 boost of some element, it doesn't that all of the drugs into the
09:46 you get protected only certain things that allowed to pass and have transporters that
09:51 small or that are like a filling designed to pass through the blood brain
09:56 , allowed to pass other things are and kept within the blood. And
10:02 uh in some instances blood brain especially if you're talking about neurological pharmaceutical
10:12 can become an obstacle. Why is an obstacle? Because most of the
10:20 are kills that gets swallowed, it through your digestive tract, a fraction
10:26 that active ingredient gets into your bloodstream then from your bloodstream, a fraction
10:32 that active ingredient can cross through the brain barrier. And if you have
10:37 example, if you're watching some commercials Tv and they're talking about antidepressant drug
10:44 PTSD post traumatic stress disorder and they're all of these side effects. So
10:53 you take this drug you know it help your depression, you will help
10:56 PTSD but you will have abdominal maybe abdominal bleeding rashes on the
11:03 Okay, what what why are you all of these things? Because these
11:07 side effects. These are side Because you're taking a drug you're targeting
11:13 condition in the in the brain but receptor, similar target molecules and cells
11:18 also found in the body. And a fraction of that drug will cross
11:23 the blood into the brain. So designing a neuro drug, a good
11:30 drug or a good molecule, you to keep this in mind and the
11:37 that we want to do in this is have neural drugs that can cross
11:43 blood brain barrier very efficiently. So should be small. You hear about
11:49 medicine, nanoparticles, making things nano maybe they should be like a
11:57 so they dissolve through the membranes and into the brain ultimately you want that
12:04 to bind to specific cell subtype. we know that specific cell subtypes like
12:10 example pyramidal cells in hippocampus and pyramidal are in the cortex and there throughout
12:15 brain? So you're still going to all of the parameter cells. But
12:20 if you guys got so smart and advantage of those cellular markers that are
12:27 to the cells and somehow managed to the drug to that particular cell subtype
12:33 a particular part of the brain. is really the ultimate that we want
12:37 do. You want to get as to the problem as possible if your
12:41 is being generated from the temporal lobe the side and you have a clear
12:46 that starts the seizure, Most of drugs will treat the entire brain,
12:52 that area, but ultimately what we is to get the drugs that are
12:57 specific and that can easily cross the brain back. It also brings a
13:03 . It's like, well, what the other delivery methods then? This
13:07 quite inefficient if we're swallowing tail. other delivery methods like inhalation, what
13:12 in your lungs almost immediately goes into blood. There's an advantage to speed
13:17 to get things into the blood. other things, nasal sprays. We
13:23 about substances crossing directly to the So for certain conditions and not just
13:28 sinus uh information for epilepsy for there are some nasal sprays and this
13:35 something that I think is going to explored more and more. It's just
13:39 the hat we are the creatures of now carrying a nasal spray to spray
13:45 I'd rather just, you know, and take the pill. Um,
13:58 , I mean, we it's it's getting there but it's not to the
14:03 that that I'm describing where you'd be to identify cell number 17 in the
14:09 and target that salad, avoid that 17 and other parts of the
14:13 So not to that extent. But definitely being, you know,
14:18 you know, the cells that have in oncology themselves that would be recognized
14:24 they're mutated and they have certain There's a certain extent, yes.
14:29 to the extent that I'm talking about more of a sci fi and and
14:33 solution for the center and really, , so we are moving on to
14:44 of this good staff that we Okay. And today we're gonna talk
14:51 resting membrane potential and what is resting potential. I explained to you these
14:58 , electro physiological recording techniques where we little electrodes and those electrodes can be
15:03 inside the cells. So when you an electrode, this micro electrode and
15:09 have this micro electrode outside the I'm gonna say that outside of the
15:13 environment is grounded or it's zero, no charge. It's charge neutral.
15:21 as soon as you cross the membrane neuron, your volt meter will show
15:28 drop to about -65 million poles. we know that neurons are excitable.
15:37 also know that muscles are excitable. know that there's a charge separation,
15:42 unequal distribution of charge on the inside the cell verceles outside of the south
15:47 all of the action in the membrane near the membrane, all of the
15:53 accumulated. The negative charge on the The core inside of the cell is
15:59 neutral. So only the outside edges the membrane is charged -65. And
16:06 outside is positively charged because we have charge, we have the ability to
16:14 ions across plasma membrane in a very fashion to produce this very fast action
16:22 . So when you talk about action , this is active member and
16:26 And when we talk about resting membrane , they're called passive membrane properties because
16:31 cell is not actively producing this action . But we're talking about excitable
16:38 And before we talk about wrestling number potential, we're gonna remind ourselves of
16:44 of the activities. And the reason you need this fast activities and fast
16:50 in ions is because we have to not only to uh sensory stimuli coming
16:57 , but also motor stimuli, You want to jump out the bears
17:02 at you. You want to not there and think although sometimes, you
17:06 , you don't know what to do the bears coming after you sometimes maybe
17:09 it's good to stand, you watch videos of the bears. Uh people
17:16 the trails hiking and come across the and some run and some just stand
17:21 wait to see what happens. But any case if you step on the
17:25 , you wouldn't think for long. you put your hand over something
17:28 you wouldn't think for long intellectually. this really causing my skin to melt
17:34 not? Is it really painful? this reflexive behavior? So you need
17:38 reflexive behavior. Reflexive behavior that we're to discuss today is the simple reflex
17:44 , the simplest part of our simplest of reflex pathway. And this kind
17:50 a test that is exhibited here with stimulation of the attendant here is performed
17:58 the doctor's office. So even if go to see your primary care physician
18:04 an annual checkup, he or she do that. Put a little mallet
18:09 your patella tendon, tap it. the effect should be that your leg
18:14 up a little bit like this. normal hotel attendant reflex, arch,
18:22 , knee jerk, reflex stretch or tendon. It's all interchangeably used.
18:28 the stimulus here, there's a little , a little mallet, neurologists will
18:35 that for sure. Actually doctors will it when the kids are growing
18:39 You know, they'll have them follow pen with their eyes and check everything
18:44 this reflex to So when this tap here, this information at the level
18:52 the quadriceps or extensive muscle, that's muscle that's going to kick up the
18:56 . So if the contract is going kick up the leg, you have
19:00 root ganglion cells. So take good here because you already know that dorsal
19:06 ganglion cells a pseudo you Nicole Like we talked about morphology, these
19:14 neurons have a peripheral axon, peripheral will pick up mechanical information, mechanical
19:25 tapping here from this area. This axon will send the information into the
19:31 dorsal root ganglion cell selma's that are outside the spinal cord. That's why
19:37 form that ganglion that bundle. Because Soma said that, and then there's
19:42 much through the central axon. So is studio una foto sell through the
19:47 axon. It's an excitatory cell. is going to release glutamate onto the
19:56 neuron here. Motor neuron is a cell that we discuss morphological and
20:05 This motor neuron will cause the release acetylcholine by motor neurons at what is
20:13 a neuro muscular junction neuron to So just with the mama synaptic
20:22 this self except the sensor activity exercise glutamate motor neuron motor neuron releases the
20:29 locally and this muscle will contract. a very reliable synopsis, a very
20:35 synapse. The charge for the synaptic is very high in amplitude. So
20:41 always have a twitch. If this activated and the motor neuron is
20:46 you will have a contraction of this . However, we know that when
20:51 select your biceps, what happens to triceps, it's relaxed, it's the
20:57 muscle action. So when you have contraction of your quads here on the
21:06 for the reflex to be effective and your leg to effectively move up and
21:12 you actually have to relax the For the flex a muscle hamstring will
21:20 if you're bringing it in now you to relax this muscle so it just
21:24 what you're activating. In this case activating the contraction off the quadriceps.
21:31 do you relax the hamstring? So this reflex to actually be effective you
21:39 have to involve a local interneuron in spinal cord. So when the same
21:45 neuron is excited will release glutamate on inhibitory interneuron here. It's also a
21:52 cell and this inhibitor interneuron will release inhibitory neurotransmitter and it will inhibit this
22:01 neuron and by inhibiting this motor neuron motor neuron is not releasing any acetylcholine
22:08 the muscle is kept relaxed so that can have a proper contraction of the
22:15 . One thing to note that's very to data said that the major excited
22:20 your translator of the CMS is The major inhibitory neurotransmitters. Gaba gamma
22:25 butyric acid. These inter neurons in spinal cord they release glycerine. So
22:33 the neurotransmitter they release. This is exception in the sense of exception to
22:39 in the C. N. S the spinal cord glycerine is an inhibitory
22:45 that gets released by these multipolar into . Okay and inhibit in this case
22:52 hamstring motor neuron relaxing the hamstring in words is mono synaptic single synapse
23:01 Is it enough to contract the Yes it is. But is the
23:06 like it's going to be fully effective relaxing the hamstring? No. And
23:11 do that you're now looking at policy circuits because it's multiple synopsis that are
23:18 . And it's still a very simple synaptic 123 synapse circuit. Some of
23:24 complex reflexes that we have that involves synapses and sometimes different parts of the
23:31 of the brain I can think of example as a gag reflex. Uh
23:39 something if you inhale or if you something nauseous or even emotional response could
23:48 a gag reflex that it's a reflexive . You don't control. Many synopses
23:52 be involved in order to execute That would be more of a more
23:57 reflex. So for this part please yourself you know the sensory afghans caring
24:05 into the spinal cord DRG cells, neurotransmitter, their anatomy. You have
24:12 processing in the spinal cord and you activation off the output which is at
24:21 is going in a e is going of the spinal cord into the
24:29 Um And this is multipolar cell. self inhibitory interneuron licensing, excited.
24:36 remote. Yes. Yes. Yeah it's a good question because I'll confuse
24:49 even more toward the end of this because glycerin also turns out to be
24:55 little made receptor co factor in the don't take these notes now. We'll
25:00 back to it later. Okay so as as I said in in and
25:05 every science and the Neurosciences always So this is an inhibitory neurotransmitter in
25:10 spinal cord. And slicing will serve different function in the cns. Now
25:15 is that? It because it depends what receptors are expressed by the post
25:19 cell. So the response of the will depends what receptors it expresses.
25:24 it have only excited there is an only inhibitors analysis. This is also
25:29 very simple circuit because this is excitation excitation excitation. Okay, so
25:38 build up this charge across plasma membrane creatures of water and we have a
25:44 of water in the brain and oxygen extra electrons and has negative charge,
25:51 has negative net positive charge held by bonds. Water molecules and other polar
25:59 such as ion sodium chloride will dissolve in the water and they will form
26:06 bonds and some of the ions will protons and electrons that are different than
26:16 . So some of them will have valence. Your charge mono valent charge
26:22 as chloride minus mono valent dive allen calcium two plus so the valances to
26:33 ions are positive ions, N. plus calcium two plus K. Plus
26:41 cat ions and and ions are negatively ions. So the most important one
26:47 be discussing chlor idea. And as know, neurons are surrounded by plasma
26:55 is possible lipid bi layer and this lipid bi layer as it is does
27:01 allow for ions to cross through the . In order for the science to
27:07 through the bi layer, you have have channels. And the major ions
27:12 we will be discussing over the next lectures are sodium potassium chloride and
27:20 There is an abundance of sodium chloride the outside of the South is
27:26 There a salinity environment on the outside the south and the inter cellular environment
27:31 dominated by potassium. There is very calcium inside the South there's a lot
27:38 calcium. Um Outside of the The reason why there's very little calcium
27:42 the South is calcium is not only ion once calcium enters inside the South
27:47 also a secondary messenger calcium can also calcium release from intracellular stores and activation
27:57 transcription factors. Which means it can something about the translation and transcription mechanisms
28:05 the self. That's why you don't that much of the three sides.
28:09 the calcium just floating around the one comes in typically gets bound up or
28:16 or bound up by these calcium binding . So it's not just really floating
28:22 and then finally hear what you have an ionic pump and this ionic pump
28:28 a K. T. P. . S. It will use
28:31 T. P. A lot of and it will always transport ions against
28:36 concentration gradient. So there's a lot sodium fluoride on the outside. So
28:43 a high concentration gradient of sodium and concentration gradient on sodium on the
28:47 But this pump will be putting sodium concentration gradient, putting potassium inside the
28:53 against concentration gradient by using energy in form of A. T.
28:59 Uh So these channels that will allow passage of the ions I made out
29:07 the building blocks the nino assets that like a high school teacher and some
29:14 them are essential and that is not and essential amino assets you have to
29:20 . They come from food and others have in our bodies but they're building
29:26 , they make these peptide bonds and building blocks for the proteins to form
29:32 through these peptide bonds and you have lot of them. So it's called
29:36 peptides. And this is a primary of these amino assets. And then
29:43 secondary structure would be that you can this chain of amino assets and you
29:47 make a coil out of it almost a corkscrew. And this is called
29:53 alpha helix. And it's a secondary and also take these strings of amino
29:58 and you can lay them as sheets you will hear their referred as beta
30:04 . So there will be a helix there will be sheets. There will
30:07 other secondary structures that you can find the secondary structures will form a
30:14 So several of these alpha helix is can be trans membrane segments. Several
30:22 these trans membrane segments will form a subunit and then multiple subunits will come
30:29 and form in this case a channel some of the channels uh some of
30:37 uh ion channels that you're seeing here , some of the protein receptors are
30:42 not channels that could be g protein receptors but they'll also have a certain
30:47 composition. And certain anatomy says all complex strings of immune assets and the
30:56 ordinary structures finally form the channels and channels are specific to each eye
31:05 So as you can see, sodium have its own sodium channel and it's
31:11 to control the flux of sodium potassium have potassium channel, calcium, calcium
31:17 chloride. Some of these channels are fast. It's called conductance. How
31:26 of an eye on how much of charge can you pass through the
31:30 So some of them are fast and acetylcholine receptor channel can conduct a million
31:38 a second. So that's current I million islands a second. That's a
31:43 . That's very fast conductance. It's fast and very large amplitude change at
31:49 level of the plasma membrane, some things and other processes. We already
31:55 hope everybody's tweaking onto this That you several temporal scales in the brain.
32:00 have these very fast neurons and then have these super fast neurons and slower
32:06 . Then you have these slower glial . They don't fire action potentials and
32:10 produce calcium waves. And they're concerned with homeostasis, metabolism, inflammation,
32:19 processes. And at the level of membrane, you have some channels that
32:23 fast, open fast, close some are slow. You have to
32:28 of wake them up for them to . And when they open close and
32:34 can be slow to using energy and slowly but steadily pumping against concentration gradient
32:43 and potassium. So channels are selected filters that means that they will accept
32:50 ion sodium channel except the sodium ion it will kick out, potassium ion
32:56 not allow for potassium ion to come . And when these islands come
33:00 they're surrounded by these waters of hydration we called by water molecules. And
33:06 they're entering into what is called the inner lumen of this channel against
33:12 they're losing these waters of hydration and this most narrow point here there are
33:19 acid residues and so as positively charged such as sodium or potassium will have
33:27 negatively charged amino acid residue. So amino acid strings that you have some
33:33 them may have positive charge on the . Studies will have negative but inside
33:38 of the channel for sodium will have charged residue. And there's actually going
33:43 be a little bit of an interaction allows a very quick binding of the
33:49 and propulsion of that sodium molecule into inside of the south and surrounding or
33:56 it with the water sub hydration. it says loading the strip of the
34:01 by amino acid residues enters inside the diameter potassium was trapped and sent back
34:09 . Huh? So that should make think. Does that mean the channel
34:15 ions based on their size purely? it partially the answer is is
34:23 partly on the sides. But you to recall one thing is that sodium
34:30 a smaller ion but sodium will have stronger attraction, smaller ion for more
34:38 set hydration. So it's slightly different dynamics that these ions will have.
34:46 no, it doesn't mean that sodium pass through potassium channel because potassium channel
34:52 bigger. potassium channel will regulate and selective to potassium. And then at
35:00 point, all rules are broken. do I mean by all rules are
35:06 . There's inflammation in the brain hyper , epileptic seizure activity, all the
35:15 are open things are gonna be crossing they can cross And that will depend
35:20 much on the size them. when the rules are broken, the
35:24 becomes an important factor. When the are there normal physiological conditions you have
35:31 interactions of ion the size the waters hydration, the specific amino acid residue
35:37 the binding properties that are designed for ion to selectively control one single ion
35:45 that channel? A little bit of . Right here we have the equals
35:54 arms law. Very basic review where voltage and bolts and for neurons we're
36:01 about miller balls. So the relevant is miller voles current in amperes and
36:08 neurons it's nano amperes, PICO In some instances, micro amperes resistance
36:17 is measured in arms and neurons are small, only 10 micrometers in diameter
36:23 they have high input resistance. So have high resistance which is measured in
36:28 homes, tens and sometimes hundreds of arms conductance is an inverse of
36:35 Existence of G is equal one over . Or R. If you rewrite
36:41 formula V equals IR I is equal times v conductance over change over voltage
36:49 conductance is measured in cement and the scales for neurons is nano and PICO
36:55 . So conductance is how much a ion channel conducts, how many ions
37:00 can conduct. Or let's say overall to the whole cell because the cell
37:05 have 2000 channels each with a specific value and then maybe you can multiply
37:12 2000 ad 2000 to get the whole conductance of the entire cell. What
37:20 some of the forces that determine this of charge across plasma membrane and some
37:27 the basics that we're going to review based on the concentration. If we
37:32 look at the concentration gradient, which the amount of that molecule, the
37:39 of that molecule. And if you a possibility by layer has no
37:44 everything will stay on that side. when you introduce the sodium channel,
37:48 introduce the chloride channel, the plasma . And if the rules in neurons
37:54 purely based on concentration gradient, then sodium and chloride ions will flow to
38:01 opposite side until both sides become the concentration or equal molar. So these
38:08 you see that an A plus is and then in a plus and an
38:13 plus become exactly the same. Chloride chloride become exactly the same concentration.
38:21 , so diffusion forces. So if have a lot of concentration of one
38:27 and little on the inside and that is gonna try to come inside the
38:32 is going to drive that ion across membrane. However, ionic movement is
38:38 by the electrical potentials because ions are and voltage and voltage changes are going
38:50 determine also very much not only the of potential, but also how much
38:55 an ion is passing through. So have cat ions, positive ions and
39:02 will be repelled by an ode or other positive ions by the positive charge
39:08 they're going to be attracted by cathode by negative charge and by subversive and
39:15 will be attracted by an oats and by the like charge separation of charge
39:23 plasma membrane. This uneven distribution of across plasma membrane is what gives rise
39:30 difference in electrical potential that we measure with these electorates addressing membrane potential.
39:37 resting membrane or VM is the same Inside charge of the cell. And
39:44 what we're measuring. Address this -65 votes. Then by convention you have
39:52 flow and direction of net movement of charge is in the direction of the
39:59 . So cat ions move with the of the current and and ions in
40:07 opposite direction. If you reduce the of negative charge compared to the positive
40:13 on the inside of the membrane from 65 to minus 60 to minus 55
40:19 causing deep polarization. There is less the polarity separation. You de
40:26 You make two sides more equal in . However, if you increase charge
40:32 and make the inside of the cell more negative than minus 65 minus 70
40:38 75 you are causing hyper polarization. increasing the difference in charge separation between
40:45 and positive on the two sides of membrane. So how does it really
40:50 like? So, first of all is really an illustration of what I've
40:56 you before this charge separation and accumulation uneven distribution of charge negative and positive
41:03 at the level of the membrane. you again looked in the side of
41:08 environment more toward the inside of the . You can see it's charged neutral
41:12 minus plus minus on the outside. , positive charge. Now the positive
41:17 negative attract each other. So they up here across by remembering and then
41:22 away in the side of in the side of solid works to settle the
41:26 . It's charge neutrality. Again, there's no charges zero. So if
41:33 was based on just concentration gradient, saw that if you have a channel
41:38 this potassium should flow across the channel you should have the same concentration of
41:44 on this other side. In this we we we we introduce an a
41:50 which is a negatively charged, let's protein. And that protein can of
41:55 or it could be an ion and no channel for that ion or the
41:59 clothes for that. I cannot cross an island but this potassium, as
42:05 can see this huge concentration of potassium potassium here, you open the
42:11 potassium starts flowing and then potassium stops before it reaches the same concentration on
42:19 opposite side. Because as potassium starts from inside of the cell to the
42:26 , this positive charge of potassium will building up on the plasma membrane and
42:34 start repulsing more of the potassium coming . This is the electrical forms.
42:42 the concentration gradient is still gonna say a lot of potassium here, go
42:46 the other side, go to the side is going to drive it to
42:48 other side. On the other The build up of this positive charge
42:52 gonna say uh we're repelling, you back, go back this is what's
42:58 the equilibrium potential that this situation, diffusion all and electrical forces are equal
43:06 opposite to each other in the direction there's no net flux of ions.
43:12 means that some potassium is going to right, some potassium is going to
43:16 left, exact same amount. There's net flux to the left hand side
43:21 to the outside of the south. this is the time and moment.
43:27 the potential value plasma membrane at which I said, the concentration diffusion,
43:34 forces driving in this direction have an repulsion of charge, electrical currents and
43:43 no net movement of charge. So have this net ionic differences at the
43:50 membrane. We will discuss this concept the driving force once you understand today
43:56 to calculate equilibrium potentials and the membrane in general, the resting membrane
44:02 So, hold that thought. But thought indicates that it has something to
44:07 with DM and E. Ion Dion the overall membrane potential. E ion
44:13 equilibrium potential. What does that mean the ionic concentration is known or unknown
44:23 . We can calculate this equilibrium potential island. Welcome back to this
44:29 M minus E. Ionic in a seconds. No it's not just for
44:37 . So the same goes for any or sodium you have a lot of
44:42 on the outside, you open the but sodium will start flowing down concentration
44:47 until the electrical potential says no So it never reaches equal molar
44:53 That's where you have the separation, distribution of charge inside versus outside,
45:00 around the memory. And in addition these channels, as you can see
45:07 certain concentration of these ions that we um in the old days we knew
45:14 concentration of ions for animals like squids example, they have these giant toxins
45:23 where do they live in the very high salinity environment you live in
45:31 you can tell what ions you have right in that water and you can
45:36 the axon and you can squeeze the out. The side is all out
45:40 axon or the cell and you can what ions you have there. So
45:45 knowing the concentrations of ions on the or the outside, you can now
45:50 the equilibrium potential as you can see outside of the cell is dominated by
45:58 and by chloride there's a lot of of the signs on the outside of
46:02 cell and there's little of sodium and on the inside of the cells.
46:10 outside of the cell also has about million moller of calcium And the inside
46:17 the cell has .0002 million mauler of . So when you talk about concentration
46:28 or inequality of concentration, the highest gradient concentration gradient is actually for
46:37 It doesn't mean that this is what's determining the member in the country and
46:43 also doesn't mean that these channels are open. Such thing that we'll talk
46:48 called permeability of these channels, but , you have a lot of
46:52 a lot of chloride, a lot calcium on the outside, little of
46:57 molecules on the inside and the inside the cell is dominated by potassium and
47:01 are the actual no um all of . Okay, And here you have
47:10 fluoride ion with the concentrations and you ride out these concentrations inside versus outside
47:17 ratios to there's 20 times more potassium the inside of the south, there's
47:23 times more sodium on the outside of cell versus the inside of the
47:28 And the other thing that is shown is -60-175. Nobody bothers to ask
47:35 about that. It's about 15, votes. What does that mean?
47:40 means that different subtypes of cells that discussed will have slightly different membrane potential
47:45 rest and that is because they all slightly different composition of these higher
47:50 These ion channels may have different sequences amino acids, which changes their
47:55 how much they can conduct. Maybe can conduct 100 110 gallons a
48:01 That depends. So what does that ? And what value am I gonna
48:06 you what's resting membrane potential minus 60 65 minus 70 minus 75. I'm
48:10 give you a whole step with diagram the values that we will follow because
48:15 textbooks will give you a different answer resting membrane potential. And that just
48:20 , it depends on, as I , how permeable are these cells to
48:26 ions And we get to that in second but also there might be different
48:30 . Micro fluctuations of certain ionic concentrations and regional. And then there are
48:37 things that are called thermodynamics. When goes up, things start moving
48:43 temperature goes down, molecules and movement ions slows down. Does that mean
48:50 we all are constantly at 37°C to physiological body and brain temperature?
48:58 you may wake up and you'll be and then by the time you had
49:03 coffee, your 37 you get in argument with somebody at 38, you
49:09 sick with fever at 42C, you to go to hospital But is it
49:14 to be always at 37. Now gonna go into a sea of body
49:19 is gonna change slide all of So these all micro fluctuations will determine
49:23 speed of movement to and that speed the temperature will influence the number of
49:29 . Now hear what you have the values or equilibrium potential for potassium
49:36 80 sodium positive, 62 calcium 1 and chloride negative 65. The equilibrium
49:46 for an ion can be calculated using famous nerves equation and what nerves
49:54 You determined that if we have the which is ionic of liberal potential actually
50:02 up with a formula. So an you're not gonna need a calculator,
50:06 gonna need to know the terms of formula. So if I write it
50:11 you should be able to recognize that have the wrong terms in this
50:16 And you should be able to recognize calculations for ions but not having to
50:22 them yourself. So what he came with 2303 R. TCF long based
50:29 algorithm ion concentration on the outside of cell which is oh and I on
50:36 which is iron concentration on the inside the self. R. Is the
50:40 constant. T. Is absolute Uh But we can also insert you
50:47 in T. When we're going is going by body temperature 37 C.
50:52 whatever you wanna do, you can into Calvin or use T. Charges
50:59 valence of the ion Plus one Plus -1. The f is saturday's
51:07 Again it's electrical constant it doesn't And then the concentration of dials.
51:13 if you take this 23 03 remember equilibrium is the balance of two influences
51:20 which pushes an island balance concentration chemical gradients and electricity which causes an
51:27 to be attracted two opposite charges and by life charges. Increasing the thermal
51:34 of each particle increases diffusion. That's I talked about. The second will
51:38 increase the potential difference achieved equilibrium. ionic equilibrium is proportional to temperature to
51:47 proportional to T. On the other increasing the electrical charge Z.
51:54 Each particle will decrease the potential difference to balance the fusion. Therefore e
52:01 is inversely proportional to Z over We need not to worry about are
52:07 . And nurse equation because there are and when you take the 2303
52:13 T. C. S. And collapse at 37 C it actually collapses
52:19 61.54 with the middle of all And then you have log of potassium
52:26 versus potassium inside log of potassium sodium versus inside florida outside versus inside.
52:34 this is all the same calculation 61 middle of balls for potassium. Same
52:39 sodium because nothing changes here is plus plus one. Okay except the concentrations
52:48 different here. But here that it's 61.54 for chloride and that's because chloride
52:54 gonna have a Z f minus So that's very easy. And for
52:58 this abbreviated to half of 61.57 which 30.77. And that is because you're
53:05 it by two here calcium is two . So you're dividing by the valance
53:11 So you can then take the potassium and potassium on the inside and hear
53:17 ratios. Remember I told you you plug in five on the inside outside
53:22 100 on the inside or you can 1-20. So here we plugged in
53:28 ratios and the outside is 1 20 more than inside this log 1/20 is
53:35 negative 1.3 and negative 1.3 multiplied by term here 61.54 million balls. Give
53:43 the equilibrium potential for potassium of minus million balls. So if we if
53:50 do the same exercise and you do calculation for sodium and plug in the
53:55 values from here 10 on the one on the inside for calcium and
54:03 . These are the values equilibrium potential that you're going to see for these
54:09 ions. Okay so this is for ions. So nursed equation or equilibrium
54:19 calculation is for single ionic species for or for catastrophe. And notice that
54:29 E. K. is -102. here the ion for potassium is
54:38 That's why I don't want you necessarily get hung up on the exact number
54:43 about another lecture when I give you actual scale, there's gonna be fluctuations
54:49 differences. Why? Because there might more of a potassium ion on the
54:54 of certain themselves rather than inside. so that will influence again the value
55:00 that ionic equilibrium potential. But what that do for us if we know
55:07 equilibrium potential for one ion? Do know the resting membrane potential? We
55:13 because sodium will flux, potassium chloride will flux calcium influx. So
55:21 membrane potential as we see it at is not just one ion. It's
55:27 interaction and interplay of the ions that dominant here sodium potassium chloride,
55:34 And how do we calculate the membrane ? To calculate the number of
55:39 We're using the golden equation and the equation after this part here is exactly
55:47 same as nerves equation. This T. Z. F. Log
55:52 our TCF collapses 61.54 million goals. have a log something new here.
56:00 of all, you have potassium on outside and inside. That's the same
56:04 Newton's equation. But now you have ion that you're taking into consideration and
56:10 sodium multiple ions. The other thing is different is the P.
56:18 Which stands for permeability is it's not uh analytical chemistry PK value. Its
56:24 for podcasting. How much is the permissible to potassium addressing number and
56:34 The cells have these ion channels for that are called leak channels and they're
56:42 be leaking potassium out. So like why are they looking? Because that's
56:47 the nature built it has a lot potassium and potassium is slowly oozing out
56:52 the cells addressing members potential. That that the cell membrane has mostly potassium
56:59 opened And other channels like sodium channels not. So that means that addressing
57:07 in potential there's huge T. permeability value for potassium. 40 times
57:14 permeable to potassium addressing number of potential to sodium. Does that mean sodium
57:21 not flexing? No but 40 times than potash in. Does that mean
57:26 sodium does not contribute to the value the resting membrane potential? No.
57:32 you're also doing the calculation of the is not just the permeability. One
57:38 something doesn't change anything. But if have a different value here with concentrations
57:44 calculation that you run through the potassium four or five. This is real
57:50 moller plugged in here instead of Like we had a nurse equation you
57:56 this, you take the log of 50/4 15 61.4 you get minus $65
58:03 . So is it the same as equilibrium potential? No not exactly.
58:09 minus. We talked about equilibrium potential potassium typically being around -80. Is
58:16 close anywhere to the equilibrium potential for ? No, but is it influenced
58:24 sodium? Yes, absolutely. So major dominant eye on address and the
58:30 is most formidable to this potassium But that changes from the ability for
58:38 for sodium or potassium chloride can change as permeability changes. Guess who gets
58:44 weight during the rising phase of the potential that will start discussing next
58:50 The cell is mostly permeable to The rules change the permeability ratios
58:57 It's just opposite. The cell becomes times more permeable to sodium. Then
59:03 during the rising phase of action potential the following phase of action potential,
59:08 changes again, it flips and the becomes most formidable to potassium again during
59:15 following phase of the action potential. , overall membrane potential at rest resting
59:24 potential. Deanna's the membrane potential it is dominated by sodium and potassium
59:31 mostly dominated by potassium flocks During the and rise of action potential. It's
59:39 permeable to sodium. And then it backing on. And so you have
59:43 flux in these ratios. Some cell a little bit more permeable to
59:49 others more permeable to sodium. And you'll get different calculation here just put
59:56 or put, you know, 145 13 and you'll see that it changes
60:03 different value minus 67 minus 63. will shift. Okay. And this
60:08 what's happening in reality. And that's when I showed you this measurement and
60:13 , nobody is asking me a question what is the resting membrane potential?
60:17 it minus 16 minus 75? So follows somewhere in between all of these
60:22 on the properties and the qualities of channel and depending how formidable the plasma
60:27 is to give an eye on at particular uh space and time. So
60:34 is actually the last slide uh and we finished for today and when we
60:43 back on Tuesday, we'll continue talking the action potentials. So we'll review
60:48 two formulas again, you don't need do the calculation, but if you're
60:54 tell me that there's way more so on the inside of the south,
60:58 gonna get the question wrong. You , if you're gonna say that it's
61:04 of temperature announced equation, you're gonna the answer on if you're gonna say
61:09 Goldman equation is only calculating based on ion from the ability. Again the
61:16 answer. So we'll review these two because a lot of stuff I think
61:21 podium structures, basic will review these equations and then we'll move into the
61:27 of the action potential and you'll understand about the openings and closings of the
61:32 and you will know more than you to know about action potential after we're
61:37 with it. So thank you very . And I'll see you all on
61:45 . Thank you guys on zoom.
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