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BIOL 4315 Neuroscience Tue Th 8.30-10am - NEURO Lecture 07 ACTION POTENTIAL II
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00:02 This is lecture seven of neuroscience and few lectures we were talking about resting
00:11 and potential. And we started talking the action potential choice. And in
00:17 when I showed you certain stimuli into south and I said these are the
00:22 stimuli and they look very square wave . And I said the cells don't
00:27 in that square wave like fashion because membrane has resisted and capacity the
00:35 So the first concept that we're going discuss today is that the plasma
00:40 whether you're talking about the resting membrane , you're talking about the active flexes
00:45 ions through the membrane, such as action potential or other conductance is uh
00:51 have to start thinking about membranes and in circuits and equivalence. What would
01:02 equivalent of these circuits and in physical electronic circuits maybe. And so if
01:11 look at the potassium channel, this potassium channel on top. Each of
01:17 channels here has a resistor. So is a symbol for resistor. Sometimes
01:32 a variable resistor that will that will an arrow through it. And channels
01:38 variable resistance. Okay, no, you were and in the physics department
01:49 that would be also called conductance, is which is G. Mhm conduct
01:56 , which is inverse of the resistance we talked about. And in
02:01 as you can see in this circuit for this channel, you also have
02:06 battery. And so this is the for the battery here. one of
02:13 ends is a positive. It's a . That's a symbol for the
02:20 These these these symbols here at the . Mhm. And so you can
02:31 that the conductance is through these channels change because the channel can be fully
02:40 . And there could be a large to the channel channel could be partially
02:44 . Will be small conductance of violence it could be closed and there's no
02:49 . So this conductance would vary the potential or the battery comes from where
02:56 battery comes from. The fact that have a separation of charge and you
03:01 electrical potential and equilibrium potential. And equilibrium potential is actually a reflection of
03:08 the chemical and electrical forces. So if you look at the conductance
03:20 , this is conductance for potassium channel or gamma. Mhm. And this
03:32 basically just rewriting alms law. V Ir you know owns law. The
03:39 force we know is D. Which is membrane potential and E.
03:45 . In this case, equilibrium potential potassium ion. So you can rewrite
03:50 Vm minus C. K. It our the gamma or giza conductance,
03:57 is the inverse of the resistance. you can have I if you have
04:03 equals Ir, then you can have equals V over R. And the
04:11 which is I is then equal conductance the driving force. So that's another
04:20 of just looking at the conducting system arms law. Uh huh. And
04:27 can have a concurrent for potassium channel is essentially what we're talking about here
04:35 the conductance times the driving force and where individual potassium channel. But as
04:43 know the cell will have many potassium . And so the conductance in the
04:50 cell or across all of these channels depend on the number of potassium channels
04:57 are in that piece of the plasma . So the total conductance will equal
05:02 number of potassium channels and the conductance that potassium channel. And again this
05:10 conductance. So it can be It can be smaller depending on the
05:15 of the situation and the plasma Mhm. So the main three channels
05:21 the plasma membrane that we talked about would influence the number in potential the
05:27 potassium and chloride. Remember that a member and potential neurons are leaking to
05:35 . That's just the rules that exist potassium channels neurons are open, the
05:42 is leaking so potassium has high permeability rest. Mhm. Remember that each
05:49 of these ions will also have a . But because of the separation of
05:56 on the opposite side you can see the battery sides, the capital and
06:01 all sides are different, more sodium they are for potassium. Just because
06:06 have a lot more sodium on the and for potassium you have a lot
06:10 potassium on the inside. So the of the battery are reversed. But
06:15 one of them have the battery and conductor. So when I showed you
06:25 injections into the south and I said when you inject the square way plus
06:33 this is something that you would inject electronics? Mhm. But the response
06:40 the cell looks something like this. not square wave. And this is
06:47 membrane properties because of the membrane This is the electronic circuit switch on
06:52 off. And this is a And the important thing about the membrane
06:58 that the membrane also has capacity of . And this is a symbol for
07:11 . Right? So that means that you inject the current into the cell
07:24 on the A. One on the which is electronics. The cell you
07:29 see response with this kind of a response. And why is that?
07:35 you have to build up the The charge doesn't immediately cross on the
07:40 side of the membrane. De polarize cell. It slowly builds up.
07:44 does it in a very fast fashion milliseconds but it's not instantaneous. And
07:54 cells are very good capacitors. Capacitors are possible lipid biologics are really good
08:03 because in order to have good capacitance , you have to have a lot
08:10 surface area where you store the The two plates of the capacitor.
08:15 positive and negative should be very close each other. And in this case
08:20 just separated by a possibility by The other thing is the charge and
08:26 discharge should be quick. So you be able to charge up and discharge
08:31 membrane in a in a fast And this is qualities of a good
08:38 . And so the cell has both and capacitive properties. If the channels
08:42 not open the resistance is high, channels are open, the conductance will
08:50 , the resistance will go down, will increase. Huh? But then
08:56 have capacity so you have to rebuild charge. And when you de polarize
09:00 cell you slowly build up discharge within . And when you stop the stimuli
09:06 can see that the number of potential again and it relaxes over a few
09:13 of time. So the response from cell is never a square box unless
09:18 measuring individual ionic channel conductance is that a little bit more square wave like
09:28 . It's, so the other thing each one of these channels has their
09:39 properties I. D. Properties current properties. There is a relationship between
09:47 and the amount of current in this , what you're seeing is an Amish
09:54 or linear relationship meaning that for 10 of all change in one direction or
10:03 mil level change in another direction. amount of current whether it's positive or
10:08 was equivalent was the same. These would be referred to as ivy plots
10:18 voltage Current plots and each one of channels will have its own line and
10:31 of the channels are not linear. these I. D. Plots would
10:36 different for different channels. So hang to the ivy plots because we will
10:45 back and talk about that ivy plots the in the in the following lectures
10:50 thursday where I have a a good I want to walk you through.
10:56 but this is the current voltage relationship the channel. Most of it is
11:04 linear. Some of it prefers to conducted in the outward direction. Other
11:09 prefer to conduct ions in the inward . Go ahead. Okay the channels
11:19 open. You said that when the are open capacitance will decrease.
11:34 You open the halls and you're not as much charge actually. But its
11:39 increases and decreases are more correlated with secular fusion. The neurotransmitter released on
11:47 on a much more stronger relationship and the openings of the channels. But
11:54 the resistance for the internal resistance of cell depends on resting channel density.
12:03 it's not only whether the channels are , it's also how many channels you
12:08 ? How dense is the population of channels? Small neurons will have high
12:13 resistance because input resistance is the membrane divided by four pi times radius of
12:25 spiritual neuron. So the smaller the of the sparkle neuron the larger than
12:35 resistance. So the smaller than neuron other words, the larger the input
12:41 , the larger than neuron, the of the resistance. The change in
12:50 can also be viewed as a change charge over the capacitor. So just
12:59 of the charge over the capacity of and the input capacities is dependent on
13:11 membrane area. But instead of being by the radius of of hysterical
13:19 you actually multiply four pi times the squared. And so the larger the
13:30 , the larger the surface area, more capacities you have. So if
13:35 think that if channels are open now punched holes in the capacity of plates
13:41 much larger changes as I mentioned, be associated with the secular fusion where
13:45 actually increase the surface area of the membrane when the vesicles fuse is and
13:51 you decrease it a lot more significantly just punching little holes. Okay,
13:58 the resistance is dependent on if it's small neuron it's high resistance. If
14:07 a small neuron it is low capacitance there isn't as much of the service
14:15 . So these are the membrane equivalent . I put this empty page so
14:19 you can be able to identify these on the exam and then you can
14:29 start building the circuit or drawing the . So you would see this in
14:34 physics department engineering electronics, you have sodium conductance potassium chloride, they have
14:44 own respective batteries. You have the side of cellular side, the current
14:49 flow would get redistributed through these Okay now you have passive and active
14:56 is so for example in chloride right if you look at this diagram there
15:01 no arrow and there is no I there is with sodium so there's no
15:07 of sodium fluoride. Right now sodium flexing from outside and two inside because
15:14 have sodium chloride that's very concentrated on extra cellular side. And potassium is
15:21 from insight into outside because you have concentration gradient driving potassium and also the
15:27 channels. This is a representation of pumps. Remember that the pumps will
15:32 work against the concentration of iridium. it will always bring sodium to the
15:36 and potassium to the inside. And is a really full complete representation of
15:43 member in circuit by incorporating the capacitor in the plasma number. So this
15:53 really neat because you have a You actually can program it in the
15:57 and you can play with different properties the conductance is through different channels of
16:02 capacitor and their models. The computational models that allow you to do
16:08 And you will say, well we're aside because it's really good because if
16:12 remember when we talked about X ray , it used to taking a five
16:19 to solve the structure of on program now it takes 25 minutes of artificial
16:26 running on sophisticated computers to spit out same information. So if you have
16:34 basic circuit then you can play with basic circuit just like you know when
16:38 mechanics kind of popular mechanics you connect current flows, it doesn't the battery
16:44 . And then you can build a more sophisticated circuit and you can have
16:48 really sophisticated model. And this is plasma membrane. And then somehow you
16:53 think of, okay, well can actually then computational e study different conductance
16:58 in what they do to the membrane , firing frequency of the action
17:02 Yes. And you can study how cells communicate with each other. So
17:07 are complex models that are somewhat accessible user friendly. And then a lot
17:12 it is obviously are complex circuits that have to build on your own if
17:17 want to investigate certain properties of the and certain properties of the cells and
17:22 so on. So, uh this a quick reminder on the two equations
17:32 we looked at. We looked at nearest equation and Goldman equation. And
17:37 when we looked at the Goldman I said that That resting membrane potential
17:43 you can see here potassium with one at 0.04 chloride, that .045
17:55 So this is permeability ratios of potassium resting membrane potential and sodium addressing member
18:02 potential. You can see that the ratios switch completely. And during the
18:08 potential which we were discussing last the cell becomes most permeable to sodium
18:14 . So during the rising phase of action potential The cell is 20 times
18:19 permeable to sodium as it is to . And notice that addressed chloride His
18:29 . And during the rising phase of actual control Florida's .45. So the
18:35 is permeability is for these ions and charged ions. They don't really change
18:41 much in this respect. The greater of particular ion and greater its member
18:47 permeability the greatest role in determining the number of potential. So recall that
18:54 there's a lot of some ion and is driven across and if the membrane
19:00 permeable to that ion then the overall potential will start getting biased. Cover
19:06 equilibrium potential to that given ion. . Thanks. Mhm. This is
19:18 diagram that I'm going to use when ask you exam questions because if you
19:22 on your slides in some Slides, on the same slide, it says
19:27 potential for equilibrium potential for potassium is And some slides say it's -90 and
19:35 slides that say it's -80 and this not a trick question and I wouldn't
19:43 you two To to ask you is really -90 is in -85 -87.
19:51 textbook will have a slightly different There are slightly different calculations that happen
19:58 e and then there's actual data from recordings, there's a discrepancy maybe in
20:03 few million volts. Their cells are . The local environments are somewhat different
20:08 . But just recall that this diagram all of the necessary components that you
20:12 to know and understand about the equilibrium for each child, calcium, sodium
20:21 , potassium Resting membrane potential. Remember membrane potential is really not -65.
20:28 just fluctuates You have action potential which is negative 45 million volts.
20:37 so once there is enough excitation and to input and the membrane potential which
20:43 VM. When the number of potential the threshold for action potential, it's
20:49 or none. Events. In other , if membrane potential climbs to -45
20:55 cannot just come down and go to again, it has to go through
20:59 cycle of the action potential at this at the threshold. First of
21:05 when the cell d polarizes, you up sodium channels, the sodium channels
21:12 up more sodium comes in more deep . So it's positive feedback cycle.
21:19 because the cell is most permeable to . So, do you mind,
21:23 trying to drive the membrane potential VM its equilibrium potential value over here,
21:29 55 million, it doesn't reach the potential value because that these deep polarized
21:36 , there's a great difference between VM potential and the equilibrium potential for
21:44 So that means that there's a huge force when the membrane is d polarized
21:49 potassium and that driving force for sodium the sodium equilibrium potential is here.
21:54 driving force for sodium. It's not great anymore, it has actually
22:00 And now there's another feature here, first of all an increase in driving
22:06 in potassium. That's why the member potential starts falling again. And the
22:11 factor are the dynamics and the kinetics voltage gated sodium channels. Those are
22:17 channels that despite the positive feedback cycle open and they closed the transient
22:24 They open very quickly and they close quickly because they have gates that open
22:30 , activate them and gates that close or inactivate them. We'll discuss that
22:35 a few slides. So during the phase of the action potential, it's
22:41 potassium that takes over and potassium is to drive the member in potential to
22:47 own equilibrium potential down. But here starts encountering an Ak pumps that are
22:55 against concentration gradients. And at this here, the driving force for potassium
23:00 very small. So the leak currents still there and would still be leaking
23:06 resting and below resting membrane potential. the driving force is not big at
23:11 . So now the member and potential re polarizes And if again, there
23:17 a deep polarization to the threshold it will produce the action potential during
23:22 absolute refractory period. You cannot produce action to control. And that's because
23:27 the kinetics of the sodium channels. the sodium channels open and closed and
23:32 , they actually the membrane has two polarized. Those channels are dependent on
23:37 . So depending on where the voltage , the channels will be open closed
23:40 do something different. You cannot evoke action potential. But once you cross
23:45 this falling phase back the threshold plan action potential generation in this relatively factory
23:52 . Now you can you have a enough stimulus, you can produce an
23:56 to control yourself. So the frequency the action potential will very much vary
24:02 the strength of the stimulus that is into that south and how long the
24:06 refractory period is going to be. some membranes have slightly different kinetics and
24:13 . And they have longer refractory They have slightly different composition of member
24:17 channels and others and others have shorter refractory periods which make them fired higher
24:25 . Had the ability to produce higher um patterns of the action potential
24:32 Thanks so the concept of the driving . Remember it's the difference between the
24:39 . Number and potential N. E potential for potassium E. For sodium
24:46 for chloride individual islands as it relates the overall numbering potential. Okay we're
24:58 watch a movie of how it all . How these recordings of action potentials
25:06 . It's a quick movie if I get it to start to play.
25:11 hmm. The careful airpods, body and habits are so very different from
25:19 of humans that there might almost be from another world. So it's too
25:25 , huh? In the safe? hmm. But perhaps it's not
25:43 right? Give me 1 2nd that took a long time. Mhm.
26:06 , the careful airpods, body plans habits are so very different from those
26:10 humans that there might almost be aliens another world. So perhaps it's not
26:17 that it took a long time for to discover that there are fundamental similarities
26:22 the nervous systems of cephalopods and mm hmm. Yet it was the
26:30 of a useful difference in their nervous which enabled scientists to undertake research that
26:36 led to a growing understanding of the controlling our own nervous system. The
26:43 concerned the nerves that control the contraction the mental muscles used in jet
26:51 As this archive film shows by simultaneously it's mental muscles. Even a moderately
26:57 squid can inject a huge amount of with great force. Yes, in
27:06 mid 19 thirties, the british zoologist James Young was engaged in a study
27:11 the squid's anatomy. Young observed an of large tubular structures, each as
27:18 as a millimeter in diameter in the mantle, as these structures were never
27:23 with blood, they could not have blood vessels from their similarity to surrounding
27:29 fibers. Young thought they must be neurons, giant axons. They're transmitted
27:34 impulses from a concentration of nervous tissue estelle, a ganglion to the mantle
27:45 . Using electrodes, he stimulated the nerve fibers and found that he could
27:50 produce large muscle contractions in the mantle the large tubular structures remained intact.
28:02 these were indeed giant axons. Scientists appreciated the significance of Young's finding.
28:12 here at last was an axon, and robust enough to investigate with the
28:17 available at the time and one that for several hours when isolated from the
28:27 , the intracellular contents of the giant could be removed and analyzed, leading
28:32 the discovery that sodium ions were more outside the nerve cell and potassium ions
28:38 concentrated inside. So this is exactly we talked about. How do you
28:45 the concentration to calculate the equilibrium for . This goes back to this original
28:51 , you isolated this one millimeter And that's huge. We're talking about 10
28:57 diameter neurons. It's not a giant that swallows the ships. It's a
29:03 large squid but it has a giant in it. Um And the environment
29:10 lives in saline environment, it's different what our composition is in the
29:16 it's a lot more salt in the than we have in our physiological uh
29:26 . But if you squeeze it you can now measure different concentrations of
29:32 . Using other techniques Also, you tie one end of the axon and
29:40 a dye in it and see how die gets transported. What's the speed
29:46 that transport? Mhm. By refilling empty axons with solutions of precisely known
29:54 composition, experimenters were able to unravel mechanisms of iron transport across the
30:05 The myelin axons are large enough and enough for fine electrodes to be inserted
30:10 the cell membrane and into the axa . In these early techniques a fine
30:22 tube was first inserted into the axon secured with threats. Then the tube
30:48 used to introduce a fine wire electrode which the voltage between the inside and
30:53 outside could be measured. But the of the Nerve Impulse was far too
31:00 for detailed study with any of the measuring devices of the late 1930s,
31:06 wasn't until the 1950s following the wartime of electronic equipment such as the cathode
31:12 Oscilloscope, that major progress was Scientists found that the nerve impulse was
31:21 as a characteristic wave of electrical potential that this all or nothing action potential
31:27 generated mainly by transient movements of sodium potassium ions across the nerve membrane.
31:37 on the squid giant axon unravel the of the formation and propagation of the
31:42 action potentials. This understanding led directly the development of drugs that block action
31:49 formation and so act as local anesthetics used routinely as painkillers in dentistry and
31:55 surgery. Friends would walk up. know that when we look at the
32:03 potential, we look at the conductance we know that the resting membrane
32:08 potassium conductance is much greater than sodium is the leak channels. We know
32:14 during the rising phase of the action you have a much greater sodium
32:21 The potassium conductance of sodium ion sire ng on the falling phase. This
32:29 again the conduction rules changes the cell becomes most conduct it'll to potassium over
32:38 and that's what causes the number of . You go down to the equilibrium
32:42 of catastrophe and also undershoot undershoot the membrane potential. Remember under shoots because
32:50 potassium is driving it below The resting potential of -65 to its lower value
32:57 its own equilibrium potential. And of that when you have rebuilding re polarization
33:04 of the member of potential to the potential value. Go back in the
33:08 situation where the sodium islands are are . Now when you're recording member and
33:21 and you have an electorate in the . This is the traces that you're
33:28 is the trace of the VM of overall number and potential. But what
33:33 want to do is you want to isolate individual ionic currents. We want
33:41 isolate sodium card. You want to potassium card. You want to just
33:47 sodium current. You want to study the sodium channels. Just the
33:51 just the calcium, whatever it may , the answer is just the chloride
33:56 . How do you go about doing ? Uh There's a technique called voltage
34:00 technique and this diagram looks somewhat But the questions that I'm going to
34:09 on this are going to be good you follow through what I'm going to
34:15 to you is the basic concept, concept of voltage clamp. This is
34:21 squid giant axon. So this is our cell nerve cell here and we
34:28 the reference electrode. This green reference is just the ground electrode. It
34:35 it's zero because the ground is Ground is charge neutral. Outside environment
34:41 the cell is charge neutral, so zero. And then you have one
34:46 electrode that you insert here. It's . And that internal electrode measures membrane
34:52 VM. And so it sends that to the amplifier and displays it on
34:58 sill a scope on the computer screen the membrane potential from this neuron through
35:04 green circuit here on the left. it is connected to voltage clamp.
35:11 . Alright. And number two, have the voltage clamp amplifier located here
35:19 member and potential to the desired command or command voltage. What is command
35:26 ? Command voltage. It's whatever you to make it. When you sync
35:33 electorate inside the cell and you stimulate cell you get the cells response action
35:41 . But wouldn't it be nice to the cell membrane? I want you
35:45 be minus 90. I want you be at positive 20. I want
35:52 to be a positive 55. How you do that? And the way
35:56 do that is using voltage clamp. Now in number three, If this
36:03 in potential, let's say, your voltage that you said is -90
36:09 I'm commanding this cell membrane to be -90. But if the cell numbering
36:16 because it received an excitatory input, cell numbering is going to try to
36:21 from -19 to maybe -80 more positively . So this DM Becomes different from
36:29 command potential. That's the difference I it at -19 And I'm holding it
36:36 . The cell receives a positive Who wants to go to -80 and
36:40 the difference. Now, that's the . So the clamp amplifier injects the
36:45 into the axon through the second electrode through this orange electorate. This feedback
36:52 crosses the number of potential to become same as the command potential. So
36:58 time you said I want to keep at 90 -90 positive input -80.
37:03 voltage crime bible of fire says no . I'm clamping you you're holding or
37:10 the number and potential. But the is at a certain remembering potential value
37:17 -80 positive for me. Whatever the that flows back into the axon and
37:23 across the membrane is measured here. that means that everything that is different
37:31 what you said it to be If it goes to -85, the
37:36 is gonna measure five million volts of to drive it down to minus
37:42 And it's gonna measure that there was change in the current of about five
37:47 volts which is the inputs currents, currents other south communicating through the south
37:53 are coming in. Yeah. And difference is gonna be measured in either
37:58 or negative. Yes, that's So it could be it could be
38:03 actually could be setting it at Positive and the cell is going to negative
38:10 and you keep dragging positive 40. you can go either direction on the
38:15 . Yeah. Yes. If the is -90 and it goes to my
38:31 would be plus town. But if from 80 -82, -90 would be
38:36 town. Yeah. And you would up whether it's a positive or negative
38:40 flocks and then you will know whether an inward or outward current movie.
38:45 , very good. So you can that these are some of the experiments
38:56 if you do a small deep you have capacity of current and you
39:00 a leak current and you have mostly conductance is if you have large deep
39:06 you will increase the capacity native and currents and active voltage dependent conductance
39:13 So when you de polarize the cell lot, you will get this kind
39:18 a response. If you're using the clamp measurements in reality what the action
39:27 is. It's the sum of the currents that are early that are followed
39:33 the outward currents. The inward current the sodium moving inside the cell.
39:39 by convention is actually a negative current and the outward current is potassium positive
39:46 moving outside the south. Okay. this is the deflection here for potassium
39:54 . So if you look at the potential, where's my action potential?
40:11 , wow. If you look at action potential on uh Thanks.
40:41 We know that this is dominated by in parents but we know that this
40:48 dominated by potassium currents. But guess ? There is an overlap on these
40:55 these currents that are happening in Okay, so this would be your
41:01 con and this would be your potassium number and potential represents a collection of
41:10 . It's a reflection of sodium and ions But the two overlap in
41:17 And so if you look at this Hodgkin and Huxley used the voltage clamp
41:23 isolate individual currents. If you put voltage clamp of minus 80 million volts
41:31 minus 90 million volts in this you put the voltage climb with minus
41:37 million balls, What is -90 million . Its equilibrium potential for potassium.
41:44 you be able to record any potassium of mindless Sadie There any driving force
41:51 potassium at -90? I mean No. Mhm. So would
42:02 What would you study if you had holding potential of -90? You would
42:06 the other currents. Mhm. So and Huxley used this voltage clamp
42:14 Use this voltage clamp technique. And is the early current that's inward
42:19 This is the sodium current. And is the late current and that's the
42:24 current coming out and that's the potassium . And so they d polarized the
42:30 membrane in the voltage clamped, clamped to -26 million volts. The resting
42:35 potential is -265. But remember the clamp, you can command the membrane
42:42 . So they commanded the member and to be -26. And what they
42:48 as they saw this small inward But that inward current turned on turned
42:55 and it was followed by an outward . You do polarize the cell to
43:02 . What happens to the sodium driving ? It's increasing, right is a
43:11 current for sodium at zero mil levels minus 45. Yes, the sodium
43:18 sodium or deep polarization. So you see that the inward current has increased
43:24 at zero mil of Ulster is a driving force for potassium and you can
43:31 that now the outward potassium current has increased. You go to positive
43:39 What happens to your sodium current? it getting larger? It's getting
43:45 Why? A positive 26 sodium current smaller? Because it's reaching the equilibrium
43:53 for sodium and the driving force for is decreasing. And also the
43:58 As you learn, sodium channels are . What's happening to potassium outward current
44:04 positive 26. It's huge. The current is huge because there is a
44:09 driving force for potassium. Mhm. happens at positive 52. Mhm.
44:18 inward sodium carl? Is it It's gone. Why is it
44:27 Its equilibrium potential value for sodium? no current flux and current flux.
44:33 no there's no there's no net Blocks one Direction of the Atom. What's
44:40 on with potassium currents? It's Right? Because of these deep polarized
44:46 , it's positive 52, sodium has driving force, equilibrium potential and potassium
44:52 a huge driving force. You go positive 65. Where is our sodium
45:03 ? You see this little blip This is now sodium current, but
45:10 in the opposite direction. Why is an opposite direction? Because you crossed
45:17 equilibrium potential value. So that's why potentials are also referred to as reversal
45:24 because the current will reverse and start in the opposite direction, this is
45:28 physiological, this is done with voltage but as you surpass, as you
45:36 the equilibrium potential value into more positive above the equilibrium potential value for
45:43 Now that sodium instead of coming in cell is actually going to flexing outside
45:48 yourself. So you don't see actually inward current, but you see a
45:53 small outward current and once again this , persistent long potassium current that these
46:02 polarized potentials. So Hodgkin and Huxley this voltage clamp technique In 1963,
46:10 won a Nobel prize in physiology and for their work in action to
46:16 And they even have a Hodgkin and model for action potential. That has
46:22 interesting parameters that basically allow you to this action potential. Did you have
46:26 question? Thank you because sodium is through the positive feedback loop. So
46:46 more channels that are opening. So conductance has increases until about it reaches
46:53 positive values here. Positive 10 positive 26. And you can see
46:58 sodium current and starts decreasing. This the the phase of the action potential
47:15 If this is zero line here, the year sodium is coming in,
47:22 coming in but here you can see driving force for sodium which is
47:28 it's decreasing. So if you come , this driving force is going to
47:33 smaller and the current is going to smaller and the second thing is going
47:36 be the closing of the of the of the sodium channels. So they
47:40 transparently the open, open open and they start all closing and that's why
47:44 starts decreasing. Both do the closing the channel and due to the lack
47:48 the driving force for that island sodium , sodium channels have a structure where
48:02 have for trans membrane subunits and each of these sub units 1234 has six
48:12 membrane segments As one as 2 as as 4 or five. And a
48:18 S four segment is a voltage sensor . So it has all of these
48:24 charged amino acid residues in between Five and the six. We have
48:30 hairpin loop that roderick Mackinnon was described the potassium channels. And you can
48:37 that this poor loop from each subunit come inside the channel and be the
48:44 selectivity filter inside the channels for these . It also shows that the sodium
48:51 which are in action potential. We're about both educated sodium channels, They're
48:56 by voltage and you can see this charged sensor. Mhm Plaza november in
49:19 is negatively charged and so this vaulted which is positively charged. It's actually
49:27 and it's negatively charged inside of the number. But once there is deep
49:33 , what happens is the positive We'll start replacing the negative charge and
49:39 positive charge build up. Well actually start retelling the motive center. So
49:47 is a three dimensional structure. And this voltage sensor gets repelled by positive
49:54 of this deep polarization is a sodium , it slides upwards. It changes
50:01 confirmation of the three dimensional structure and up both of these channels. So
50:08 is how the sodium channel opens. two gates and both gates open and
50:16 open and they immediately close. It's inactivation and that's another reason you can
50:24 the sustained stimulus here on top of deep polarization and this is the opening
50:29 an individual sodium channel. And despite deep polarization which you had the lock
50:35 the membrane potential of positive 26. this deep polarization, sodium channels open
50:42 closed. There's a very transient. fast opening. They're fast inactivating because
50:48 have this gate that will swing them . And then in order for you
50:54 restructure the channel, you have to polarize the plasma membrane in order for
51:00 channel to be closed and ready to opened again. So these are the
51:05 of sodium channel that determined basically why peak of the action potential doesn't reach
51:14 potential sodium channels start closing and also driving force start decreasing. Sure,
51:21 gonna leave it here today. And we get back On Thursday, we
51:28 review one more time the sodium channel potassium channel dynamics. The different recording
51:37 . We will talk about great Toshio Narahashi in his experiments with
51:47 And then we will dedicate about half hour or so talking about the back
51:52 action potential. And then you're class , you will have the information about
52:04 back propagating action potential. So if want to read up or if you
52:09 to have a high resolution figure with full figure legend, it's it's here
52:13 you. So thank you very And I will see everyone on
52:18 I'm going to try to wrap up save the lecture. If anybody has
52:22 and come up and feel free to
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