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BIOL 4315 Neuroscience Mo Wed 4-5.30pm - NEURO Lecture 06 RMP II and ACTION POTENTIAL I
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00:03 This is lecture six of neuroscience and discussed the major ionic species and how
00:12 ionic species have their own concentration That means that there is a separation
00:19 charge across plasma membrane. The cytoplasmic aside of the possible little by layer
00:25 negatively charged and the extra cellular side the fossil lipid bi layer is positively
00:33 . The inside of the cell as as the outside environment outside of the
00:37 are charge neutral. So this charge is really persistent along the phosphor lipid
00:45 layer. Do you have positively charged that are cat ions, negatively charged
00:51 that are and ions? And in to their concentration gradients, meaning in
00:58 to high concentration through diffusion, all driving that ion into low concentration areas
01:05 plasma membrane, each island carries a . And because of that charge there
01:11 an interaction with the other charges that accumulated on the plasma number. Um
01:18 ions will be attracted to the negative of the battery cathode and an ions
01:24 the ponder pole of the battery or . The difference in the member and
01:30 is the difference between the outside and inside of the plasma membrane. And
01:35 this is an example where you have ion that has very high concentration on
01:40 side of the plasma membrane and a charged ion. And you can say
01:46 a negatively charged ion, it could negatively charged, large protium that doesn't
01:50 plasma membrane and there's a specific That specific channel is specific to
01:56 sir. And potassium channel opens even this is another ion, it may
02:02 have a channel that's open for that . So the channel is open for
02:06 and the first thing that happens to is the concentration gradient. The diffusion
02:10 forces will drive potassium ions across the membrane to try to equalize the concentration
02:16 potassium on both sides. But after positive charge starts accumulating on the right
02:22 of the membrane right here, that charge becomes repellent to further potassium crossing
02:30 plasma membrane. At this point, chemical forces driving potassium from high concentration
02:37 low and electrical force positively build up on the plasma membrane which is repelling
02:44 become equal and opposite enforced to each . And there's no net flux of
02:50 , ions will still be moving inside outside, but they will not be
02:54 toward the movement Into one direction or other. So at this at this
03:01 an ion reaches its equilibrium potential value stands for here for e ionic
03:10 ionic driving force depends on the difference the membrane potential and equilibrium potential to
03:18 given ion. So what do we to know in order to know the
03:24 force and why is this driving force ? So you may not have heard
03:28 concept before, but the driving force really responsible for driving the ions and
03:33 across two plasma number into certain member potential levels. And if the ionic
03:41 of these islands are known, we calculate the reversal potential or the equilibrium
03:47 . So I use the equilibrium potential the ionic interchangeably with the reversal potential
03:53 me and for most of the scientists and reversal potential, it's the same
04:00 , the same concept that we're How do we know the ionic composition
04:06 the South? So in the middle the 20th century, people have picked
04:11 big squids from the ocean and they where squids live in the ocean.
04:17 you could tell the salinity level of and all that ions and the seawater
04:23 you could take this big sound, axon and actually squeeze it out
04:28 And then you could measure what the of ions are inside the self.
04:33 in these previous diagrams that we talked already, when we talked about the
04:39 of charge, we already saw that is a discrepancy in in in in
04:44 science and so sodium is the same . sodium is on the outside and
04:50 will follow its concentration gradient and once encounters its own electrical potential repelling
04:58 it will reach equilibrium potential for So, these are the major ionic
05:04 , sodium potassium, calcium and You have a lot of sodium chloride
05:09 the outside of the South, so saline environment, it's Aquarius saline
05:14 Salt, sodium chloride and you have lot of potassium on the inside of
05:19 South, each one of these ions a certain concentration as you can see
05:25 outside in mila moller and concentration on inside of the cell. In mill
05:30 too. So you can express this spike miller moller on the outside or
05:36 million moller on the inside. Or can express it as a ratio There's
05:42 more times of potassium on the inside opposed to the outside. If you
05:49 at the sodium you have 100 and millimeter on the outside and 15 millimeter
05:55 the inside so that can be expressed a ratio of 10 times more sodium
06:00 the outside as it is on the . And this is for calcium and
06:07 the same thing. But notice that highest disparity in the concentration gradient,
06:14 of all of these four ions exists calcium two plus there's 10,000 times more
06:25 on the outside of the cell than is on the inside of the
06:31 That means that calcium has this massive gradient that will be at just a
06:39 second. This calcium channels open that drive that calcium inside the cells.
06:45 that's really important calcium when it enters neurons, it can cause more
06:51 It can act as a secondary It can also promote plasticity inside the
06:56 short term plasticity and long term But too much calcium inside the south
07:02 cost toxicity. That is known as toxicity. Your calcium dependent toxicity and
07:08 kill the cells. So inside neurons inside cells calcium is not just floating
07:15 three sides of solid calcium. It's all bound up very tightly controlled by
07:21 and calcium binding proteins. But now can see the disparity here in the
07:28 gradient as it exists, the highest for calcium. I also noticed that
07:34 , which is 80 pes pump essentially always work against concentration gradient. So
07:42 the fact that there's more potassium on inside than outside, it will always
07:47 bringing potassium on the inside will always taking sodium to the outside of itself
07:52 its concentration gradient. So now we these concentrations of ions and the
08:10 And the last column here it says is the equilibrium potential values for E
08:16 for different ions. And you can that each ion has its own ironic
08:23 , potassium is -80. sodium is 62 here, Calcium is positive 123
08:31 fluoride is Momo 65. So physiologically has a certain dynamic range if this
08:40 -65 million balls which is our arresting and potential. So yes, deep
08:47 , right? You have glutamate coming , you have hyper polarization, this
08:52 gather inhibitory inputs coming in. Doesn't stay still. It walks until
09:01 receives a strong enough there. But it reaches the threshold value for the
09:07 potential and produces an all online response the form of the action potential.
09:16 how does this this numbering potentials numbering is not one eye on value.
09:22 all of these four ionic species that looking at that will contribute to this
09:28 potential value. The V. Of membrane which is measured in milli
09:37 Yeah. And to do that we to know the membrane potential value and
09:46 need to know that equilibrium potential Because if we know the equilibrium potential
09:51 and we know the number of potential we can then calculate the driving force
09:57 is the difference between the member and and the equilibrium for a given
10:02 Huh. So now you have no equation that allows you to calculate these
10:10 potentials. Use this uh 2.30 Huh. Times are T over ZF
10:22 log of 10 ion concentration on the of the cell versus ion concentration on
10:29 inside of the cell. So T. And zia. What is
10:39 ? It's gas constant. T. absolute temperature. And these measurements are
10:44 at the physiological temperature 37 C. . Z is the valence or the
10:54 of the ion. So And a is one calcium two plus Z valances
11:03 . F is electrical or Faraday's So this value doesn't change to 303
11:10 that's what nuns calculated and derived this by. And if you take this
11:15 Tze and plug in the gas which we don't have to and you
11:21 not need a calculator in order to questions and the exam about nerds and
11:26 also about Goldman equation. But you have to know all of the things
11:30 we're talking about. Now there's a of potassium on the inside. So
11:34 I give you an equation that it a lot of potassium on the outside
11:38 say this is a round calculation for , pardon me. But you will
11:43 have to do the actual calculation the . So if you take the 2303
11:48 you plug in the gas temperature the for potassium, which is plus one
11:54 the Faraday concert Constant. This to or 3 our TCS collapses into
12:02 And you gain the mill evolves value , right? And then you have
12:09 log of the concentration of potassium on outside versus inside The same collapses for
12:17 to 61.54 because everything is equivalent for and potassium here, the valence is
12:25 same plus one. So the value the same. Huh? Well it's
12:31 the same. Other concentrations are not same. That's what's going to determine
12:35 equilibrium potential. That for chloride it's negative 61 because when you do this
12:43 TCF calculation, you plug in minus here And so you abbreviated to negative
12:52 and then again it will depend on log in the concentrations And for calcium
12:57 abbreviated to 30.77 which is half of and it's half because here for the
13:08 value you would be plugging in two and dividing it by two essential.
13:13 , it's a diving bell and part . Great. So we have the
13:17 abbreviations here, we've calculated 61.61 point minus 37 7. And now we
13:23 these ions potassium sodium chloride, calcium we can do two things. We
13:29 enter these values five On the outside 100 on the inside or we can
13:37 the ratio values 1/20. So when go down here we plug in potassium
13:44 the outside versus inside is 1/20. we take a log of 1/20 we
13:50 negative 1.3. And if we multiply abbreviation 61.54 for potassium 61.54 times 1.3
14:05 , It gives us a value of monologues. And so this is the
14:10 potential value that you're seeing here. of me for potassium mines Notice also
14:19 you look in different textbooks or even in the same textbook but in different
14:26 , sometimes resting number of potential value be listed at -65. Sometimes it
14:31 be looking at the -70, sometimes -67, Sometimes -75 potassium equilibrium potential
14:39 will be listed in minus eight and 85 minus 90. Sometimes, why
14:44 that? Well, it actually The measurement depends because some cells will
14:50 slightly different local concentrations of design. ? So that's that's that's one reason
15:01 ah So you have the equilibrium potential -8. And AM I going to
15:10 you on the exam and saves equivalent for potassium -82? Or is it
15:16 sodium? The equilibrium potential value textbooks say positive 62 and most of them
15:21 say positive 55. So, am gonna again try to trick you
15:25 No, try to select the questions will very clearly indicate either the values
15:32 what I'm talking about. And in I have a separate diagram prepared for
15:36 with the equilibrium potential values and the potential values in your lecture notes and
15:41 is what I'm going to ask you . I'm gonna go by getting your
15:48 to those questions from. So we in potassium and we calculated -80.
15:54 we plug in sodium we're going to a reversal potential of 62. And
15:59 I say it's in different textbooks and slides and look at this, this
16:03 on the same slide Equilibrium potential facility the 62 And equilibrium potential for sodium
16:10 56, wow, not a trick . Not a reason to be worried
16:16 not not trying to confuse anyone This is just how it is those
16:23 theoretically this is the formula. But experimentally you think an electrode in the
16:29 membrane, it could be a difference 34 million goals. And so you
16:32 to explain that difference somehow. And this is why it is a little
16:37 different in different textbooks to So once calculate all of these plug in the
16:44 you get the values for potassium sodium , then chloride equilibrium potential or reversal
16:51 values. But that's for one. so you know from one eye on
16:57 where these forces are going to be and opposite to each other, the
17:01 and the chemical forces that still does give you a membrane potential? That's
17:06 value for one ion. And membrane is dependent on several of these
17:13 So, to calculate the member in , we use Goldman equation. And
17:20 nurses equation, golden equation notice it two differences. First of all,
17:26 not just calculating the same abbreviation is , Our TCF that collapses to 61
17:35 million volts log. But instead of taking the concentration from one aisle,
17:41 potassium, you're now actually summing the of sodium and potassium and you can
17:49 chloride and calcium into it if you to. So how is nonstick waysh
17:54 different from Goldman equation learns equations for ion. It's E. Ion.
18:03 Goldman equation is the calculation of the potential and this is the calculation of
18:09 number of potential address. And notice in the Goldman equation you have one
18:15 very important variable which is P. it's not P. K. Like
18:22 analytical chemistry, this is permeability. permeability for potassium P. K.
18:29 for sodium D. N. At rest. But resting membrane potential
18:37 are most permeable to potassium. There a certain design in the south and
18:43 the brain circuits and the design of is that neuronal membranes are leaky at
18:50 membrane potentials and they're leaking to So potassium at rest is 40 times
19:00 times more permeable. This is the value of 40 for potassium and this
19:05 the concentrations this is five million Moola 100 million mal. Again you can
19:11 in the ratios 1/20 40 times more potassium with wrestling member and potential than
19:20 . So when the resting number and is fluctuating is walking around this value
19:26 -65 or -17 different textbook -75. another textbook. What is it
19:34 It's walking along this value. It's changing because there's constant changes in permeability
19:41 different ions. Maybe thermal dynamics are across the plasma membrane, encouraging some
19:49 to open a little bit more. it's fluctuating all the time around this
19:55 MB value at rest and it's most to potassium and potassium is leaking out
20:04 the cells. So, you may how come chloride is not included in
20:10 calculation? How come calcium is not in this calculation. Remember that
20:17 What is permeability? Permeability means that channel must be open. It doesn't
20:25 how much concentration you have, it matter how many people you can pack
20:29 this room. If you're gonna lock doors, nobody's gonna be able to
20:32 out. But the concentration gradient is be huge here and people who want
20:37 get out. But until you open doors until you open the channel,
20:42 islands are not flexing. Uh So this permeability ratios changed very much
20:53 the activity changes. But the fact the matter that if you along this
20:58 membrane potential value, you can go and plug in chloride into these
21:02 go ahead and plug in calcium and will see that those two islands virtually
21:07 no permeability addressed. And if their for permeability is close to zero,
21:16 not gonna significantly alter the final calculation the number of potential value that you're
21:22 here. So, yes, it's permissible because those channels are not open
21:34 channels are there. But this is neuronal rule, you will hear about
21:39 channels. So leak currents and those currents are specific for potassium and because
21:45 is loaded inside the cells, it's of oozing out and because it's oozing
21:51 and because it's most permissible to potassium that the potassium Reversal potential here it
21:58 -102. You see the discrepancy and it shows -80. Again, this
22:04 not to confuse you but it's really the negative potentials, it's below the
22:09 membrane potential value. Okay. But fact of the matter is that if
22:14 will again, these two ions and of them has reversal of positive 56
22:20 , another one reversal at minus 100 80 you will say, well it
22:25 fall somewhere in the middle we're summing but it doesn't because potassium channels open
22:31 from the ability is increased and the overall membrane is driven down to these
22:36 polarized potentials that are close to the potential for potassium. Now, these
22:48 when you have increases in local ionic or local concentrations of neurotransmitters such as
22:59 , the brain is very dynamic but also very balanced within this dynamic
23:05 And whenever there is an increase of the system reacts to. And this
23:11 an example of what happens at normal conditions You have $5 million dollar potassium
23:19 the outside And you raise that concentration outside potassium concentration to 10, what
23:28 on the Y axis, to the VM which is a membrane potential
23:34 overall membrane potential value and this shows if you increase extra cellular potassium concentration
23:41 if you increase it to some 10 million you're actually gonna de polarize the
23:48 to ask the threshold value for the potentials. So increasing outside potassium concentration
23:55 de polarize the overall member and potential it will stop the potassium from leaking
24:01 the cells because now it's going to concentration gradient on the outside of higher
24:07 . In many experiments you will read potassium stimulation was used to stimulate the
24:13 or potassium chloride and a lot of experiments is because you want to stimulate
24:19 cells. You want to get a of activity in the south. If
24:22 measuring something, you want to detect , maybe it's a little bit of
24:25 . So you want to really stimulate in order to detect that little bit
24:29 something. So astrocytes as you recall part of the tripartite synapse gli ourselves
24:40 they have very extensive processes and their are wrapped around the synopsis and the
24:47 increases local, increases in ionic concentrations increases in the neurotransmitters local. And
24:55 there is an increase of potassium of potassium concentration, these exercises will slurp
25:03 up and will spatially buffer it by this high potassium bionic concentration, this
25:13 region through its own extensive as specific essentially will dilute potassium through itself and
25:23 through the interconnected astra sites. So we study neural transmission, you will
25:30 about electrical gap junctions and extra sides interconnected with other astrocytes with these electrical
25:38 so they can pass currents very freely between the cells. So ostracized will
25:44 this function of essentially spatially buffering and these local networks from high potassium
25:52 which can drive the member and potential up and produce abnormal activity and abnormal
25:58 in the cells firing of the action and recall that astrocytes also have their
26:06 feed on the blood brain barrier So they sense of all of these
26:11 , the synaptic environment, the microvascular and have the ability through this interconnected
26:17 and extensive processes to clean things dilute them, keep them at
26:24 I think the bible for another So this is a reading from your
26:33 the path of discovery the atomic structure the potassium channel. And it's really
26:38 story about Dr Roderick Mackinnon and so you have a book, I would
26:44 you to read this exert because there's lot of signs in here. But
26:51 really a personal story and I retell story. I don't want to read
26:57 . And so maybe I make some as I retell the story. But
27:00 me example of roderick Mackinnon is an of an individual who is driven by
27:08 quest and the passion to answer a . And it's not driven by the
27:15 and the degrees and the awards in of being passionate and driven to solve
27:23 question, he receives the awards and accolades and the recognition forever, Roderick
27:31 is a medical doctor at Harvard and very interested in the channel physiology.
27:39 when I told you, you there were in 1960s and 70s is
27:43 people started talking about these protein receptor and like I said, there's 23
27:49 in the room, everybody else would talk about something else. So,
27:54 Mackinnon, you know, and the and 90s is really interesting, really
28:00 to know the function of these but also the structure of these
28:08 And as a medical doctor, he that he is gonna pursue uh lab
28:15 where he is going to studying uh channel and to study the potassium
28:23 What we talked about is you have three dimensional sequences amino acids, no
28:32 quaternary temporary structures really complex. But do they exactly look like? Which
28:38 is important if you look at the , you know which part is going
28:45 open the door, It's the knob can push on the rest of the
28:51 on the top on the bottom. if you don't turn the knob,
28:54 door is not going to open. which part is the most important for
29:00 the door? It's the knob. part is the most important for closing
29:05 door, wow, Something that pushes door back and it's the knob again
29:13 goes back into place, right? a lot that closes it. So
29:17 the same way are these channel They're huge. They're really complex there
29:23 a city or let's say it's a , it's like this building,
29:27 And you can do a lot in building. There's a lot of amino
29:32 in the building, but different His story's second level, third level
29:39 basement, there's a power plant energy . So this is really like what
29:48 channel looks like. It's like a for one south Looks like a building
29:54 one channel is like a classroom. matter what analogy you use robert Mckinnon
30:01 that there is demeanor acid sequences and wants to know which ones are
30:06 Which ones are gonna be like that on the door, which ones are
30:09 open the channel and close the How am I going to go about
30:13 this? I'm gonna use side directed to genesis. I'm gonna target certain
30:18 in this channel. And I'm gonna electrophysiology. So pharmacology and side directed
30:26 to genesis is genetics and I'm gonna pharmacology. I'm gonna use toxins while
30:32 toxins like spider toxins, they're very molecules, they'll buy into very specific
30:38 from these channels. Nature is very . So toxins from spiders, venoms
30:44 snakes, ah toxic substances from bacteria the fish, clown shells, they
30:52 to the same channels that are present fruit flies and those channels that are
31:00 . And fruit flies we'll have a amino acid sequences. That's why when
31:05 do an experiment on the flu fruit and you're genetically manipulate potassium channel in
31:10 fruit fly and when you do that manipulation and it gives you shaker flies
31:18 is a model for epilepsy and And it's a model potentially movement disorders
31:25 Parkinson's too. Then you understand that I use side directed me to
31:31 I'm going to direct a specific sequence a toxin. It binds to that
31:38 bound to the door but it didn't anything to the door. Wrong wrong
31:44 . Next I'm going to try this . Boom toxin. Another toxin.
31:51 maybe number seven boom that one bound the door, closed the door.
31:56 found the sequence that was most important that toxin. How do you measure
32:02 the door is open or closed So measure the currents. If the
32:09 is open the current is flowing if affect the opening enclosures of the doors
32:13 going to affect how much ions are through the channel sol everything that we're
32:19 about. Great so he seems to unsatisfied. He's using all of these
32:28 experiments then he says I'm going to another career the third one X ray
32:36 . So from being an M. . And going into genetics,
32:42 neural pharmacology he says I'm going to into X ray crystallography an X ray
32:51 . People looked at him and I it was in the late nineties it
32:58 very difficult. You have to do ray crystallography or do nothing else.
33:04 other words this is the science that need full dedication to. You have
33:09 isolate that protein of interest and then have to trap that protein of interest
33:15 the crystal literally the crystal and then gonna shine X ray light through that
33:22 . That's why it's X ray It's an X ray that shines through
33:27 crystal and as it shines it exposes the X ray the structure of that
33:35 that ion channel. So that was on for a very long time.
33:43 last year when the computer program an intelligence program came out and said that
33:51 can solve the protein structure much better all of the PhD is experimenting in
33:58 labs around the world much faster and a greater accuracy without using any experiments
34:06 on the known upon it forces composition amino acids structural and sequences that we
34:16 and all the other data that has done to date. Obviously data that
34:20 Mackinnon was paving the way too late intelligence takeover these experiments and now can
34:28 the structure of the protein is better the next week crystallography. So why
34:34 I like the story because the man visualize is the atomic structure and solves
34:42 structure the potassium channel. And he that the inside of the potassium channel
34:51 this poor loop which is the selective for potassium that we discussed. Because
34:56 on our selectivity filters they see through they have amino acid interactions inside these
35:05 luminous of the channel. This is beautiful structure that he published. So
35:11 a number of techniques that go into the structure but it also takes a
35:17 person to do that. And the why I like roderick Mackinnon's story is
35:24 he was told by his colleagues that out of mind out of his
35:29 What are you doing here indeed. know practice medicine, potassium channels and
35:37 . Schacher flies, what's epilepsy Right. And then X ray
35:45 Are you not? It's like I'm gonna just go work in Nasa
35:48 fly to The you know the shuttle in their mid 40s or 50 early
35:57 . In the end. He is by the quest the quest is to
36:00 the channel structure to see the channel and he pursues it independently of what
36:08 say and independently a comfortable position or salary or a medical degree.
36:16 D. Versus PhD doesn't he doesn't care about that. You know sometimes
36:22 have a lot of degrees and I this market I had a J.
36:27 . M. D. M. . H. D. All I
36:28 is a J. O. You know, it's and I think
36:33 all you need is really to be by an answer the road and the
36:39 is always forward, never straight, like you drive on the road,
36:45 drive straight, always drive forward unless need to reverse somebody tells you go
36:51 , don't listen to them because that you're not turning the wheel and it
36:55 always forward and winding to the left to the right and there's a stop
37:00 and there's a traffic jam and that's career and that's your life and you're
37:04 in that traffic jam and it could frustrated. I want to quit everything
37:08 my job with my master's degree when exit out of college. You
37:13 it's it's a it's a road, a winding road and it's challenging
37:17 you know, and you just have learn how to deal with challenges but
37:20 be driven by buy something that is really driving you. It's not the
37:26 , but something that you want to in life. We want to find
37:29 answer to invent something roderick Mackinnon serves a great example of that individual action
37:38 , rising phase, overshoot it goes zero marbles falling phase that falls below
37:44 wrestling number and potentials. Undershoot sodium in potassium going out right, very
37:54 . That's like human action potential So methods for recording action potentials if
38:02 collect an electorate inside the cell, will record about 100 million volt action
38:08 and you don't have that much of to use. But if you record
38:13 potentials extra cellular early, that means can use electorate sort of like
38:18 not necessarily poking the cell, but of listening from a distance to the
38:23 . Then you will see that these potentials on the outside different shape when
38:29 recorded. Extra cellular early and they be measured on the order of micro
38:34 . So most of the experimental neuroscience are inter cellular wholesale recorded especially in
38:45 . Most of the in vivo recordings be done extra cellular early. So
38:49 the whole grain or whole animal and salad by action potential recordings will be
38:55 done in human brains. Pre operatively the brain surgery may be taking a
39:02 because you want to see the activity neurons and how they fire action
39:06 You want to avoid the parts of brain. That may be very,
39:08 important and others that may not be important. The special woman concerns the
39:14 functions not as much maybe a perception intellectual ability. So if the cell
39:26 weak input, this input is represented . This is something that you would
39:34 through that an electrode and it looks square. This is the current that
39:39 be injected through the electorate and this the bottom is the response of the
39:43 and the response of the cell does look square because the plasma membrane has
39:49 and capacity of property. So there be a short moment to charge builds
39:53 . And when the stimulus stops here will be a short moment the charge
39:59 itself to the rest of the And so there's no action potentials here
40:05 the resting membrane potential and a member potential will never reach this threshold value
40:10 action potentials, which is approximately minus kilovolts. But if the stimulus is
40:23 and the electronics through an electrode will the larger square wave, the seldom
40:31 the threshold for action potentials and will a certain sequence of actual potential.
40:37 the stronger the stimulus, the higher of the action potentials you get.
40:45 action potentials and the frequency and the sequences and frequencies of these action potentials
40:53 information. They encode stimulus in some . Although it is not linear,
41:00 stimulus means higher frequency of action So if you're reading out from the
41:07 number of action potentials and you see frequency firing cells, that means those
41:12 active cells that are receiving a lot input and the cells that are walking
41:17 and produce one action potential and then second later another action potential. Those
41:22 not very active or they're not receiving active stimulus at that particular time when
41:27 doing them order. So the action firing rate increases as the deep polarization
41:35 and this deep polarization can be equated the strength of the stimulus large.
41:40 polarization in strong stimulus visual auditory small polarization means low levels of stimulants.
41:52 driving forces were going to come back this ionic driving forces which is DM
41:59 and potential difference with the equilibrium potential ions. Again you have the equilibrium
42:06 values for potassium. You have the potential values for sodium but above all
42:13 have this mm hmm. So this the diagram that I'm going to ask
42:20 questions on the exam And this is diagram that I'm gonna explain to you
42:25 action potentials with regard to the driving and equilibrium protections trials. So as
42:31 notice, you have a equilibrium potential potassium -94, I -70 R.
42:39 P. Stands for wrestling member and 1965. Action potential threshold value -45
42:49 balls. Is this yellow line Thank you. It's in your election
42:55 . And if you have a deep glutamate input, you will cause deep
43:03 . If an inhibitory gaba neurotransmitter is on the cell, the number of
43:08 will hyper polarize and if there is stimulation excited for a stimulation that will
43:14 the threshold at which it will produce action potential which is all or
43:21 Meaning that if you reach this value -45, you cannot just go down
43:26 walk, you have to produce an potential. It's all or no.
43:31 at the top you have here, potential for sodium and equilibrium potential for
43:39 . So if you were just to by the rule of what is the
43:46 force and that's the difference that remembered and equilibrium potential, Then you will
43:52 at resting membrane potential, which is million volts. Not withholding anything
44:00 basically. Don't worry about the premier or anything, which i on is
44:05 farthest away which ion equilibrium potential is farthest away from resting membrane potential.
44:12 answer is calcium, does that mean calcium has the biggest driving force?
44:19 does. It has a huge driving . Does that mean calcium influx ng
44:23 number of potential? No. Why channels are closed. The channels that
44:29 talking about when we talk about action , A voltage dependent channels, those
44:35 for sodium and potassium to open based the voltage, there are channels that
44:41 with voltage that we're talking about There are channels that open with ligand
44:46 chemically opening and closing channels. The that open with mechanical stimulation such as
44:53 cells and displacement of the hair cells actually mechanically open the channel mechanical
45:01 So here we're talking about voltage gated . And yes, there's a huge
45:08 force for Sonja At resting membrane potential resting membrane potential value of -65 is
45:14 far away from Soda. It's a driving force for council. It's not
45:21 huge, we're chloride at all. it's not that big for potassium.
45:26 if you just went by the discrepancy voltage, you would be again right
45:31 the highest driving forces for calcium But that's not the ion that's flexing
45:37 most because the number is leaking But what happens is that as soon
45:46 you reach the threshold, This value value tell sodium channels it's the voltage
45:53 opens the channel, This voltage So this 45 million volt value when
45:58 member in potential the young regions was million volt value tells sodium channel
46:04 It's basically saying, I'm opening you reached this deforestation of opening sodium more
46:11 polarization. More sodium coming in more polarization. More sodium coming in sodium
46:15 influx influx ng it's going in it's in from outside to inside. And
46:21 only thing that sodium is trying to is sodium is trying to drive the
46:26 potential VM to its own equilibrium potential . So, this is trying to
46:33 this VM to E. N. . It's a positive feedback loop.
46:39 sodium more decolonization, more sodium more polarization, more sodium, more deep
46:43 . But it doesn't quite reach the potential value for sodium. It overshoots
46:49 zero million balls here. So it in the positive potentials on the on
46:54 inside of the cell plasma membrane. it doesn't reach the equilibrium potential for
47:01 two reasons why doesn't reach equilibrium potential sodium. The closer membrane potential gets
47:09 the equilibrium potential for sodium. The is the driving force number one.
47:20 . And this number and potential. potassium equilibrium potential? It's way down
47:27 and now you have a huge driving for potassium when your default theorized at
47:31 levels. And that's number one number two reason it's the sodium channel
47:38 that channels open transparently. It's fast and it's fast closing. So it
47:44 for milliseconds and closes. So you open more but they will open and
47:47 open and close its followed sodium channel and we'll study sodium channel structure and
47:54 dynamics behind these gates. It has gates activation and activation. So sodium
48:01 to reach its own equilibrium potential It fails to selfishly drive this number
48:06 potential to E. N. A here. Now potassium takes of
48:12 Uh my driving force is huge over Because my equilibrium potential is -90
48:21 I'm taking over. potassium was leaky . sodium channels all open during the
48:29 phase but then they all closed quickly that's the dynamics now potassium channels saying
48:35 open now for business, we're gonna the flux, we're gonna leave the
48:41 And me potassium. I'm gonna be now, I'm gonna say member and
48:46 go down to micro Librium potential value is -90. So it tries to
48:52 it and that's why you get this with the member and potential following action
48:58 drops below resting membrane potential values. is still being driven in here but
49:07 it doesn't reach the equilibrium potential value percussion quite because sodium and potassium pumps
49:15 work against concentration gradients slowly re polarizing , Member interested member and potential number
49:23 potassium channels will be leaking here but driving force for potassium Is close to
49:34 . So it's really the interplay of equilibrium potential values the membrane potential of
49:42 cell. Whether those channels are open not, how close fastly opened and
49:49 fast they close and this is the potential. Now during this rising phase
49:59 re polarization phase you have an absolute period. So if the member and
50:07 reaches below the threshold value, this line, you will enter into the
50:14 refractory period during the absolute refractory If you stimulate that sell one more
50:20 during the peak of this action potential produced a very strong stimulus into the
50:25 . That cell wouldn't do anything. cannot produce another action potential on top
50:31 this action potential. It actually has re polarize and sodium channels have to
50:38 their kinetics that you will learn next and cross back the threshold for action
50:46 and only in this area during relative period if you delivered a very strong
50:52 during that time you would be able produce another action country. And so
50:58 on the strength of the stimulus, delay between the action potentials will also
51:04 that the stronger the stimulus, the potential frequency will be higher and the
51:09 the stimulus, the frequency will not as fast. So on the
51:18 when I ask you questions on the , but the reversals or the driving
51:26 , I'm going to refer to this And these values that I have on
51:32 because and different textbooks, you will slightly different values. So this is
51:39 is what we're going to go Mhm. And uh well let me
51:47 back to this slide right here. I think actually that we're probably gonna
52:02 here today. So what I would is that you guys review this this
52:11 ? What I drew on the board those that are on zoom is on
52:15 power point or its pdf that is the lecture notes. So if you
52:23 the close up, I think when do a close up, that's just
52:30 . Mm hmm. So, but can find it in the notes.
52:34 I'm just pointing that out that if not seeing it, I have all
52:37 this information. The thresholds and everything the notes. Does anybody have any
52:44 so far? We're done for the but we're not done with the action
52:49 control. And so if you have some things you're missing or it's
52:57 Maybe Wednesday's lecture will clarify some of things. And then for sure,
53:03 the time we come back a third , we will know everything about action
53:07 more than you wanted to. No . Okay, mm hmm.
53:30 Okay. Yeah. Okay. So does what do the floor on islands
53:38 ? They don't do much? They flex much. It's a good
53:42 Yeah. So basically the action potential starting the capacity. There's gonna be
53:47 very minded but insignificant places of of that eyes, like florida calcium
53:53 you talk about the muscle action I don't know. Maybe that's what
53:56 getting out too. But in the the cardiac or skeletal muscle action potentials
54:03 have a huge calcium component that there longer. But in neurons it's really
54:08 sodium and potassium that played the most role. And the other islands are
54:12 quite so much if yes. You to know all the four islands.
54:34 . Sorry. I'm poor hearing. So, that's why I walked up
54:39 hear you about him. Mhm. right. Thank you for being
54:45 Let's try to bring up the guys so that everybody can do better
54:52 good on the test. Have a
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