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BIOL 4315/6315 Neuroscience Mon Wed - NEURO Lecture 05 Restin Membrane Potential
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00:02 this is Lecture five of neuroscience and finished talking about neurons and some of
00:08 properties of neurons. And we started about neuron subtypes and we said how
00:15 you distinguish these different subtypes of We can distinguish it based on
00:21 We can distinguish based on excitability, versus inhibitory. We can distinguish based
00:28 projection whether they are projecting into the networks. In this case the parameter
00:33 of the hippocampus parameter cells of the york cortex will be excited to your
00:38 sells this circuit that we looked There's a lot of things in the
00:44 that will be replicated in different parts the brain. But we presented that
00:48 a somewhat simple circuit. Three layer as opposed to neo cortical circuit which
00:53 will study in the third section of course that has six layers and has
00:58 lot more complex anatomy and connectivity. this is just an introduction to how
01:04 circuits work. And in general you these excitatory projection cells and the activity
01:10 these projections cells is going to be to interconnected regions. In this case
01:15 the hippocampus there flanked by these much diverse and different subtypes of inhibitory into
01:25 and inhibitory interneuron that will all be Gaba but there will also be
01:30 They'll be different based on their morphology on the synopsis and what parts of
01:36 excitatory cells they target and also distinguished unique and for cellular markers that they
01:43 be expressing and as we discussed they also have distinct membrane produced. So
01:55 modern electrophysiology, I thought somebody was on zoom. But it was just
02:01 . Uh So these cells apart from these different morphological and cellular markers as
02:09 may and live in different locations and different aspects of the parameter cells.
02:16 also have a different dialect. And dialect is the active in this case
02:22 pattern of action potentials, that active properties. And we will be getting
02:26 a lot more of what happens for action potential to take place. What
02:32 happens at the biophysical level at the of the member in the next couple
02:36 lectures. So what questions may you from the slide? We spend
02:43 maybe half an hour, 20 minutes the slide. You can expect
02:47 Are there 21 subtypes of tyrannical excitatory ? What are they inhibit? Their
02:53 nerds and hippocampus release glutamate or Are they excited to parameter cells,
03:01 cells or their local inter neurons. of these are great questions. Uh
03:08 uh as I said some of the that we study will get more and
03:12 complex with time. So we talked the dialect of neurons. Yes,
03:22 . Or let's see I'm a schematic . The little yellow triangles are axons
03:39 and and synapses onto the parameter So these are the selma's in red
03:45 an orange, you have dendrites and little yellow cups, I mentioned it
03:50 the past. But these little yellow and thanks for asking that again are
03:54 axons and their synapses And this shows that some of them will target these
04:00 regions of parameter cells. Because if recall 90% of the parameter cells,
04:06 are going to be found in this intermodal region. So some of them
04:11 cells will target the Selma's and others target the ethical dem rights and yet
04:18 will target the basil dendrites and even axons of these parameter cells. So
04:25 can think of these inhibitory cells. not only have these different dialects and
04:30 frequencies by which they control the output the hippocampus, but they can also
04:36 the integrative properties by targeting dendrites and . Because Selma integrates all of the
04:44 and they can also modulate the output targeting the axon. So there's almost
04:50 three levels of control anatomically dendrite axons or inputs, integration and outputs
04:59 those four regions that we discussed in therefore functional domains and regions uh and
05:06 have all of these different patterns that can do that all of these three
05:10 levels and that's what makes the output comes out of the parameter cells which
05:15 just speak one dialect. Now they're controlled how they speak when they
05:20 when they can you know, really a lot. And when they get
05:26 and their activity is sequestered into the circuits. Is there some significance where
05:33 amygdala and the programmable cells are coming with it. It's it's it's it's
05:42 schematic illustration of some of the projections connectivity. I wouldn't worry about
05:46 The take home message is the parameter would project out of it. But
05:51 do recall somebody else had a really question about the circuit. So does
05:57 mean that parameter cells and inhibitory cells some common input? And the answer
06:05 yes. So these projection cells parameter when they're gonna project into another
06:11 they're gonna contact excitatory cells in the circuit and they're gonna contact inhibitory
06:19 Everything is interconnected. Excitatory cells can inhibitory cells, inhibitory cells can target
06:25 cells. Excitatory cells can target excitatory inhibitory cells. Target inhibitory cells.
06:32 So these circuits or this circuit will a common input from another part of
06:38 hippocampus that will excite parameter cells and will be excited but they will also
06:45 inhibitory cells. And the inhibitory cells in turn can control those already excited
06:53 parameter cells and they can control what of information they're gonna be able to
06:59 of that circuit. Does that Okay cool. So we moved pretty
07:09 well and we talked about the different of the inhibitory cells and how you
07:14 perform these types of experiments and then discussed leo cells, we discussed a
07:21 of de milo Nation diseases actual with conditions. We talked about uh
07:30 We talked about sharks but mary to and periphery. And we talked about
07:35 multiple sclerosis and C. N. . Condition that has to do with
07:39 Myelin Nation. This uh image summarized well all of the cells that we
07:46 about and I think maybe at this I may jump into uh this here
07:58 big review. This image summarized a about glial south and what we think
08:06 and what we know about glial And so this is a great image
08:11 label stuff. If you have it on your note or digitally write down
08:16 a strong side does blood brain Um Synopsis micro glia next to michael
08:24 you can you know activated with You know just notes that we've talked
08:30 the likud undersides, Myelin C. . S. And next to it
08:34 put Swanson smile and P. S. So you know you can
08:38 your notes like this for for studying in some of these slides um you
08:44 see my slides are not worthy. don't like to ride down 20 sentences
08:49 for you to think that which ones these 20 are important to really remember
08:53 the exam but rather to listen and realize what concepts are important. Some
08:59 that we repeat obviously and more important others. Sounds a little bit like
09:03 animal farm. But um okay so is the blood brain barrier that we
09:11 and we discussed it in the light positive control and positive checkpoints that basically
09:20 what enters from the blood into the . The substances that are meant to
09:26 the substance substances that have transporters and there are substances that are unwelcome in
09:32 brain and there are substances that we that get into bloodstream that are
09:37 And we also want to this blood barrier potentially prevent the toxicity in the
09:44 not just the blood. Uh so have the main players and the filial
09:48 with tight junctions the parasites the astra recall that during covid infections if you
09:55 significant inflammation and heavy viral load in blood you will potentially cause breaches and
10:04 brain barrier and will make the blood barrier more susceptible for allowing the virus
10:11 virus to enter. And virus has stew receptors that it can hang on
10:18 and once it enters into the brain it can target glial cells and neurons
10:25 . Okay so we also talked about fact that blood brain barrier is a
10:32 when you're talking about the drugs and if you watch commercials on tv a
10:36 of times somebody is taking an antidepressant it's a commercial for an antidepressant drug
10:43 PTSD and you're hearing that you're gonna diarrhea, you're gonna have abdominal
10:50 you may have abdominal bleeding, you start suffocating uh you may have all
10:57 these side effects and that's because you're trying to get the drugs to treat
11:02 brain. And as I explained, of the drugs we consume are pills
11:07 get broken down through the digestive digestive tract, absorbed into the
11:13 a fraction of what was entered into mouth and smaller fraction getting into the
11:19 . And so what I said is what we want. And thinking about
11:25 drugs and the future of neuro drugs they're small molecules that they're easily crossing
11:31 blood brain barrier that there potentially like so that they can cross through the
11:36 membranes and maybe their self specific to circuit specific. That would be the
11:42 . You know, we know if apply for example, nicotine will bind
11:48 nicotine acetylcholine receptors in the brain and will bind to all of the nicotine
11:54 receptors it can find in the periphery in the brain because it enters into
12:01 blood. But wouldn't it be nice you could actually not only have a
12:05 subtype of the cell but have a receptor and still have the ability to
12:11 that receptor only in sub population of . Okay, because different populations of
12:19 will express different overlapping protein channels receptors such. So that's that's where we're
12:27 with this. So it's impeding you have side effects. So thinking of
12:31 future this is what we have to about designing Really smart um drugs.
12:39 we will talk about neuronal membrane potential . And as we talk about neuronal
12:45 potential, the first thing to realize neurons is that if you take this
12:51 electors that I was telling you about glass micro electors and you say that
12:56 outside of the cell is zero. of also neutral environment. Charge neutral
13:03 you say is grounded zero. And you pluck this electorate from this outside
13:10 that zero through the plasma membrane or a plasma membrane, the number in
13:18 on on the volt meter will show sudden change to about 100 minus 65
13:26 volts. So the reason why is inside of the plasma membrane is negatively
13:35 and the positive charges accumulated on the of the plasma membrane. Either than
13:41 the fluids further away from the member outside are charge neutral. And actually
13:46 inner core of the side of plasma the cells are also charged neutral.
13:51 the charge is actually accumulated. This separation is accumulated along the phosphor lipid
14:02 . Now we have this charge and also talked about how actions with tom
14:08 is a very fast discharge which is a very fast membrane potential. About
14:15 million volts to sell over one or milliseconds. So you learn what happens
14:21 this to happen for this action potential be generated. But before we learn
14:27 the dynamics and the kinetics of the involved in generating the action potential,
14:33 will review resting membrane potential. Before review resting membrane potential. Let's talk
14:41 the seconds and also take really good . And I'll tell you why because
14:46 gonna involve some of our favorite And if I talk about things two
14:50 three times, that's probably gonna be exam question. Okay, so why
14:56 we need the charge and why do need the discharge and the action
15:01 We need excitable tissues, It's muscle nerve. Why do we need
15:07 We need to react? We need integrate the stimuli. Think very
15:12 But we also have reflexive behaviors just the cart said that the child that
15:17 never seen the fire is gonna extends the fire and withdraw it immediately.
15:21 reflexive. That doesn't take intellect. debate whether this fire is hot,
15:26 gonna burn your skin or not. in this circuit which you have is
15:32 very simple circuit and the spinal So we're going to come back to
15:36 . And we're also going to understand differences between the synapses that are called
15:42 junctions that happened between motor neurons and and also the synapses that are present
15:50 the in the cns. So that's be the second section and we'll come
15:54 to talk about the some of the graded potentials that you're seeing there.
15:59 in general will also discuss this briefly too. Now the circuit that we're
16:06 about is the reflex arch. It's simplest kind of reflex pathway is also
16:12 jerk or patellar tendon reflex. And what is depicted in this image is
16:19 you go for sometimes you and check if your primary doctor is good,
16:25 will do this kind of thing or you complain about something in your mobility
16:32 back or something like that, they send you to a neurologist and neurologist
16:36 perform a simple test. It's a and it's a tap with a little
16:42 . Okay. And it's a tap this patella tendon here. And basically
16:49 response after that tap should be a which of the leg up.
16:54 Should be basically this circuit activated So the cap is the stimulus for
17:02 input that gets picked up by the spindle. These are sensory neurons so
17:08 will pick up that predation and sensory will pick up the mechanical stimulus in
17:14 case. Okay. And they will this information up. And these cells
17:19 dorsal root ganglion cells or DRG Yes. So if your reflex isn't
17:28 then it could be like in this there could be a problem in any
17:32 of those things. Yes, let get to that in just a
17:36 It's a great question. So the neuron will pick up this information and
17:41 sensor in Iran is excitatory and it's to release glutamate it's gonna release glutamate
17:52 it's gonna project. So this is peripheral axon. Remember this is a
17:59 unipolar style. These are great juicy because we talked about bipolar, pseudo
18:06 unipolar salsa. These are pseudo unit house. They have the peripheral axon
18:12 then they have the central axis in central axon. Remember the selma's of
18:17 roots are outside the spinal cord proper this bundle. That's why it's referred
18:24 as a route that looks like a . Ok, It's part of the
18:27 sitting there dorsal root, ganglion, DRG cells and the central axon will
18:35 stimulate or excite with mermaids the cells live in the spinal cord problem.
18:44 just by exciting one motor neuron just exciting one motor neuron here it
18:55 now tell this motor neuron to produce action potential. Okay, so the
19:01 fan goes in information processing happens you this motor neuron now contracting the quadriceps
19:10 extensive muscle. This motor neuron is to the motor neuron. It's in
19:16 neuro muscular junction and the neurotransmitter that uses is acetylcholine. Okay and the
19:27 of the salad is morphological e this self. So now if you have
19:36 contraction of the quadriceps extensive muscle, basically assuring that this reflex is just
19:43 know synaptic 11 single synapse or mono synaptic single synapse involved. Then you
19:50 contraction of the muscle but we all that whenever you contract the muscles the
19:56 you have an opposing muscle and opposing triceps. When you contract the biceps
20:01 triceps is relaxed and vice versa. you contract the triceps the biceps is
20:07 extended. Okay so you have the muscles which is going to extend the
20:15 . That's your quads and you have the hamstrings that are gonna bring the
20:21 back in. Okay. Control how of the knee is allowed to go
20:26 to. All right. So when motor neuron activates this this squadrons of
20:32 contracts but that's not the only thing happens. In fact in order to
20:37 this reflex effective and fully functional. also need to relax the hamstring.
20:45 the hamstring needs to be relaxed in for this to contract and move your
20:49 fast. So this circuit goes at some sensory neurons apart from contacting the
20:58 motor neurons here they also contacted inhibitory neurons and they inhibit the inter neurons
21:05 the spinal part are also multipolar cells the neurotransmitter that they release everybody don't
21:13 gaba it's glycerine and that's an exception the C. N. S.
21:19 the spinal cord and the C. . S. Neurons release Yabba Castle
21:27 the spinal cord into neurons release glycerine a major inhibitory neurotransmitter difference and you
21:36 know this difference. So now when inhibitor into neurons are activated. So
21:42 this sensor neuron excites inhibitor interneuron, inhibitor interneuron is going to release glycerine
21:50 this girl I seen instead of exciting flexor motor neuron inhibits the flex of
21:56 neuron and by inhibiting the flux of neuron it allows for this muscle to
22:03 . So there's no contraction there, inhibited and it's relaxed. It allows
22:09 for the quadriceps muscle to effectively pick the lag and perform this patella tendon
22:16 arch reflex. So you have the sensor information. The parent information is
22:23 the spinal cord into the periphery. that's your parent neurons apparent versus another
22:34 . Mama synaptic a single synapses enough contract this muscle. But policy synoptic
22:42 or more three is really necessary for circuit to function properly completely and for
22:49 reflex to function properly completely. Getting to your question, what if there
22:55 a problem and the patient is sitting and the doctor has to bring like
23:01 sledgehammer and the leg is still not . What is the problem? So
23:06 start guessing what the problem is? know what if what if light tap
23:11 do it but heart attack doesn't. heart attack may indicate well maybe there's
23:16 dysfunction and sensory neurons it's one thing maybe there's too much inhibition. So
23:23 there was too much inhibition then this be always relaxed. Always relaxed.
23:28 you can start looking at is it always relaxed. There is some deductive
23:35 can be done by observing this but after not seeing a normal reflex,
23:43 would have a look at it and you know they may start looking a
23:48 bit deeper into the spinal cord or like that. It could be associated
23:52 the pain that could be associated with nerve and the leg and and it
23:58 be associated with the circuit and which of the circuit. Yeah but it
24:03 give you a clue. It does you a clue. And and like
24:07 said good doctors even uh um primary physicians often do this and there's something
24:15 often do it for Children too because need to check their you know the
24:18 of the eyes and legs and feet all of that. So okay so
24:23 three types of cells in here. their neurotransmitters whether their projection cells or
24:28 they're into neurons. And how the between mono synaptic policy synaptic service.
24:35 neurotransmitters. So the sensory neuron synapses the extensive and that's where just released
24:45 good in it will be released on neurons. It will excite them and
24:49 into neurons that will excite them But those into neurons instead of releasing
24:56 on the opposing muscles release glycerine which inhibit and relax this muscle. The
25:03 basically means it just stays still. not contracting. It's relaxed and
25:13 One has no stimulation of the Yeah, but it's still this one
25:18 expresses and will release acetylcholine. Because you also need to do a
25:24 of this, you need to put leg back you know and relax
25:29 So this is just one direction. if you need to extend it will
25:35 in this way. But if you to flex this will get inhibited and
25:39 will get excited. And of course all of it is we're not talking
25:46 reflex. There's no reflex to check back circuit. Is your head giving
25:51 motor command and the ability for you do these things. But when we're
25:55 about the reflexes just to kick up it would be the same neuron,
26:00 would just have a different somewhere They're not. Or would it be
26:06 different neurons and probably different neurons and synapses. Yeah, good questions.
26:16 always most of the policy synaptic grief , we have to involve inhibitor synopsis
26:25 kerosene policy synaptic excited to uh I'm not certain if there are excitatory
26:33 synaptic reflex. And this when you about reflexes, like other complex reflexes
26:42 you're mentioning like for example gagging reflex a complex reflex but it's a
26:47 Something is toxic and pleasant. You and it activates you know, many
26:52 synapses. So that's like complex, know complex really complex reflexes. Uh
26:59 it's just by definition because its policy africa is complex so but it's not
27:04 complex. So I was excited to um in code analysis we also
27:18 Hmm. So yeah, if I'm your question correctly, so if for
27:27 , if you want to stimulate the with the light, you're gonna go
27:32 red land to thalamus once announce, actually you're gonna go through about three
27:39 in Radnor 1 to 3rd and they're and some of them will be inhibitor
27:45 the excitatory goes out of the retina going to go to thalamus from thalamus
27:50 gonna go through the primary cortex. it's already you're talking about for
28:00 yes, if you want to send long ranges you're gonna have all the
28:04 excited three circuits or networks that are processing and sending that information from one
28:12 to another from one place of the and another. Alright, so let's
28:20 for the reflex that is mediated for by the autonomic nervous system, is
28:27 the amount of while this is a of sensory nervous, this is mediated
28:34 the circuit by the peripheral, you , you're gonna involve the conscious perception
28:42 us but you won't be able to to stop it. Maybe you can
28:49 stop that. Like if you're sitting , somebody started because you're gonna be
28:53 by keeping this tight. So it's could obviously have a conscious control and
29:00 have a conscious perception of this with fact of the matter is a lot
29:03 things can happen at the level of spinal cord, Oh, reflexively or
29:12 inhibited neuron bundle, I guess they're many synapses in the or summer inhibitory
29:19 excitatory. And it's like a spatial of whether it's uh well, one
29:31 about the circuit is a very reliable . Maybe we should re examine that
29:36 . We talk about the cortical it's going to be more applicable.
29:40 is really more kind of a triangle the class, understand that there's a
29:44 circuit with one or few synapses. hang on to that thought and hang
29:49 to that question. Now, of they'll have multiple synapses. And is
29:53 an inhibitory driven inhibition? Probably to small extent. But the reason why
30:00 circuits is our reliable and why they're is the output is gonna be
30:05 It's gonna be a huge graded potential inflate potential in your muscular junction that
30:12 generated. We'll talk about it again the next section. So, hang
30:15 to some of these thoughts because you'll maybe understand it a little bit better
30:20 the next few lectures to uh so very reliable and a action potential in
30:29 motor neuron means of twitch of a . So this neuro muscular junction,
30:35 synapse here is a very reliable, fidelity. 1 to 1 I called
30:40 , okay, not so in the but we'll talk about it in a
30:45 of lectures. So let's a little talk about what's in the brain.
30:48 in general it's water, water And then some towns don't have
30:55 Oxygen attracts extra electrons and has negative . Hydrogen has net net positive
31:03 It's held by Covalin bonds. It's polar molecules like ions souls, it
31:11 dissolve ions are atoms or molecules that a net charge, positive net charge
31:19 one. The difference in the number protons and electrons, its ion valances
31:25 plus one is a positive charge or on minus one is negative charge or
31:32 ion plus two is a positive Also kati on but it's di vale
31:39 cat eye on. So you can minus one -2 to plus.
31:45 so this is for example, sodium which is surrounding the cells. And
31:50 basically surrounded by water. And you the plasma membrane. The plasma membrane
31:58 we talk, is consisting of the lipid bi layer and ions that are
32:03 the side of plasma. And ions are on the outside of the cells
32:07 freely pass through the phosphor lipid bi . So they need to have channels
32:14 these channels will control how much of major ions are going to be sequestered
32:20 the inside of the membrane versus the of the membrane. The main players
32:25 the resting membrane potential. And you'll learn an action potential but in the
32:31 membrane potential. the sodium potassium and very small extent chloride, the fourth
32:42 important ion that is shown here is . And it's not shown because it
32:48 much to the resting membrane potential. it is shown because these four ionic
32:53 are the most important for resting membrane or action potential and also for activation
33:00 some intracellular processes by calcium. Because is not only an ion inside the
33:07 , it's also a secondary messenger and can have downstream down inside the cells
33:16 processes that can activate other highnesses and associated with calcium that can even alter
33:25 transcription mechanisms and transcription outputs of the . So, calcium is also very
33:33 ion. And finally we have here potassium pump And with this shows actually
33:42 come back to this in a What this shows is that there is
33:47 distribution of these ions on the outside the cell versus the inside of the
33:53 . And so if you drop this again on the inside of the cell
33:57 measure the difference between the outside of cell to the inside of the
34:01 you will see approximately minus 60 to 75 million volt resting membrane potential.
34:10 when we start talking about these dynamics memory potential action potential. I also
34:16 some drawings that I've done myself. add these slides are already on the
34:22 notes. A lot of these slides I talk about things. But quite
34:29 there's a question to wrestling. So is wrestling member in paternity -60?
34:34 is it -75? Or is it in between? The answer is
34:41 Everything in between. Why? Why 60 to minus 75? In fact
34:48 55 to minus 90. Why? , fluctuate over time? Well,
34:57 a wrestling member and potential. but there's species of cells it's fluctuating
35:02 there are species of cells that will around -75 and others around -60.
35:09 that's because yeah, good thinking. not exactly. It's because they will
35:21 have a different composition of the ion of the possible number and expresses and
35:28 charge of the inside versus the outside dependent on the permeability through these ion
35:34 . And these ion channels could be different splice variants and different subtypes of
35:39 . And so the kinetics might be and they'll let in more ions and
35:44 instances less ions. Some cells can more d polarized wrestling number and potential
35:50 55 minus 60. And other cells have more hyper polarized numbering potentials minus
35:57 minus 80. That's for neurons and wrestling member and potential is minus 90
36:04 gallons. And you understand that in next two lectures so don't uh don't
36:09 ahead of yourself and thinking well how that happen? But the important thing
36:13 not to get hung up On the range I'm gonna be lost. Because
36:20 will talk about reversal potentials but we'll about certain values and the values that
36:24 gonna ask you to know are the that I'm going to present you in
36:28 slide because in some textbooks will say number of potential is -65 and give
36:35 the same formula for calculating it. others will say it's -70 -75.
36:41 cellular environment is slightly different to in instances there might be slightly higher concentration
36:47 sodium chloride in some instances potassium but general everything is under home a static
36:54 . And glia are really good at some of these inequalities in in in
37:04 concentrations which is ultimately means charge or in the neurotransmitter concentrations, fluctuations of
37:12 concentrations. What you were saying is different cell types, right? Is
37:18 also a range within one cell type on inhibition or excitation. So wrestling
37:24 of potential is not a set it fluctuates it's like a random walk
37:29 it doesn't deviate too far beyond like mill levels. If it deviates to
37:34 , it will produce some action potential it does have to do with inputs
37:38 in some constant excitatory inputs not constant some inhibitory input, some stronger inhibitory
37:45 and stronger excitatory inputs. Yeah, a constant, it's a constant flux
37:49 activation of difference and access. And if you reach the pressure will produce
37:54 action potential. But that wrestling number potential will never be one value.
37:58 know when you see a flatline in , bad news. You don't want
38:05 see it on anybody's monitor flat you don't want to see a
38:08 there's nothing that's bio thermal biological, no flat line. So the temperature
38:15 fluctuate around 76 but it will not always 76.0 77 78 80 goes down
38:25 body temperature same physiological. 36 37. You got a little
38:32 you know, 37 a half, know fever, 39 Celsius. So
38:37 it's a number of potential is also . It's what we call a random
38:43 will come back to that concept to affecting expression of the affecting the
38:59 Does that change expression? Um but then you were talking about like
39:09 pathology, everything is fairly balanced and this home in a static control and
39:15 we are most of us, you like emotionally contained smart but we you
39:23 have deviations and such. You we have geniuses and savants and you
39:31 pathologies too. So it's a little . Let's review the major building blocks
39:40 the cells. Me no assets. that? You need some of them
39:46 ones. You need to eat them get in your body and then you
39:53 some others. And this amino They form these bonds here and they
40:01 themselves together as the primary structure of amino acids. And they banned themselves
40:07 into these polyps peptide structures that in structures can become like helix is like
40:16 corkscrew girl and secondary structures that can the sheets a lot of times.
40:21 hear beta sheets and the proteins that laid okay tertiary structures and there's coils
40:27 their sheets could be placed in this sub unit structure and then a protein
40:37 for example or even a trance membrane coupled receptor protein will be comprised of
40:46 subunits. So then you have the ordinary structure and you will form these
40:54 channels for each ion that we talked the sodium and the potassium ions and
41:00 will be selective. So what are of the features of the ionic
41:06 First of all, some of them very reliable and can conduct. A
41:13 of ions can allow the passage of lot of ions such as in the
41:19 junction with acetylcholine receptors. Some of processes and styles are slower. So
41:26 you talk about N. A. . Or sodium potassium 80 P pump
41:31 . T. P A. They're slower. We won't conduct or
41:35 will not allow for the transport of and potassium only about 100 iles per
41:42 . So they're slower. So again have some fast processes and channels that
41:49 capable of conducting a lot and large and you have some channels that are
41:54 and they are not capable of conducting much. And they also have their
41:59 . So channels are selective filters and one of these species, sodium potassium
42:09 chloride have their specific channels. So do you when it's surrounded by
42:16 Some hydration on the outside of the will enter into the south and it
42:22 get stripped of the waters in an of getting stripped off the waters inside
42:28 sodium selective channel there is a negatively amino acid residue. We just talked
42:36 amino acids building blocks. Some of will have positively, some of them
42:40 have negatively charged amino acid residues. a very microsecond interactions. Now the
42:48 interactions with this charged polar group. this interaction allows for the sodium to
42:57 of stick to the wall of the and then get propelled into the inside
43:04 immediately gets rehydrated. Again. Now the cytoplasmic environment. So sodium is
43:13 off the waters my amino acid residues enters inside with larger diameter, potassium
43:21 strapped and sent back out so larger cell doesn't fit through the innermost channel
43:33 tries to commend but this interaction and size stops it. So does that
43:41 then potassium channel is gonna have to a bigger opening. Gas. Does
43:46 mean that smaller islands can pass. just a bigger opening. The question
43:52 , how selective are they based on and they're quite selective because if you
44:00 smaller ions will have a stronger attraction water. So they will actually be
44:07 by bigger clouds of these waters of . Number one, then there is
44:12 cell activity as it is specifically, know, related to these amino acid
44:19 . Number two. Number three. rules can be broken. Which means
44:25 at some point, yes, if is some pathological condition, if there
44:31 over excitability, even if it's transient a lot of excitability, there might
44:38 a breach of selectivity and everything maybe everything as long as the size
44:46 Mhm. But in general, the physiological conditions, These selective ion channels
44:55 sodium will patrol sodium potassium will patrol chloride will patrol chloride and it
45:01 instead of having a negatively charged amino residue and chloride channel chloride as a
45:08 and ion chloride -1, it will a positively charged amino acid residue.
45:14 may have the amino acid residue in different locations. Which also will influence
45:22 much ions or the kinetics of that , how much ions can flow through
45:26 channel or how long it can be , for example. So, we
45:29 the selectivity. It's like molecular It's not purely based on size,
45:35 size of this. It but it's it's it's dependent on science. For
45:42 . So now let's review some of basic things that you've learned a while
45:48 um swan d equals Ir where Is voltage and vaults and relevant scale
45:57 neurons. Miller vault so minus 65 volts 100 million volts neurons. This
46:05 the scales for neurons I is current amperes and from neurons irrelevant scales or
46:12 amperes and PICO amperes, resistance is is our arms. And because neurons
46:21 very small, just 10 microns in in general they have high resistance and
46:27 relevant scales and mega arms or neurons , conductance is the inverse of resistance
46:37 over r and conductance and cements the scales for neurons is PICO and nano
46:46 . And that relates to the conductivity single channels. Or overall conductivity through
46:52 whole south as a sum of all these single channels. Easy stuff.
47:00 good questions also. And also don't this very simple switcheroo here because it
47:09 keep coming up when we talk about concept of the driving force a little
47:14 later, probably next lecture now. here let's remind ourselves it's like we
47:20 this possible lipid bi layer here and we have sodium and chloride on one
47:26 and we have no channels and sodium chloride will just stay on that
47:29 So for it to to start flexing the sodium and chloride to start flexing
47:35 have to have a sodium channel. like the sodium chloride chloride channel and
47:40 will start flexing until through simple diffusion was just based on the concentration,
47:47 will reach equal concentrations on on both . So it was just purely based
47:56 the concentration, it would do that and flora, but it is not
48:05 based on the concentration, it's also on the electricity and the electrical
48:10 Its voltage, voltage and differences and in voltage is what's gonna drive ions
48:19 plasma membrane inside or outside. And you look at it, you have
48:25 battery. The negative end is a and cat ions are gonna be attracted
48:32 cathode and chloride which is an ion going to be attracted to positive and
48:39 ode. So you have apart from concentration gradient, you have electrical potentials
48:47 ions have charged plus 1 -1 to and so on. So separation of
48:55 across the plasma membrane here that we're negative charge accumulated on the inside is
49:01 difference between the voltage on the inside the outside is the membrane. A
49:07 of times you'll see abbreviation D. . VM addressed -65 million balls.
49:13 means membrane potential address -65 million bowls is the same as inside the current
49:22 . Just by definition is in the of the net movement of the positive
49:26 . So and ions move opposite because negatively charged and catan moved in the
49:35 same direction If you reduce the charge plasma membrane, that means that the
49:42 of the membrane is becoming more positive -40, maybe zero. That is
49:48 deep polarization. Your d polarizing the of the number. If you make
49:54 plasma membrane on the inside more you accumulate more negative charge on the
50:00 here, you're causing hyper polarization and arresting number. And potential from minus
50:05 can slide down to minus 70. does happen because of the synaptic activity
50:13 that does happen because of the thermodynamics local micro thermodynamic fluctuations. The warmer
50:21 stuff the faster things move. Okay and if you have a slight difference
50:27 the in the temperature across brain circuits this could be a small effect on
50:33 on the speed. So now when talking about ions because I am so
50:44 ions have what is called an equilibrium I think maybe it's hidden underneath
50:51 The equilibrium potential for e. Ionic E stands for equilibrium or an
50:58 Each ion potassium sodium fluoride calcium will its own equilibrium potential. Now that
51:07 potential best explained, is with this . So we have the potassium and
51:14 have some negatively charged sodium and we a potassium channel. So potassium can
51:22 from this inside of the south to outside of the cell. But this
51:27 is trapped there and it's keeping a bit of negative charge from the inside
51:31 the cell. So potassium from its concentration. The large K. Plus
51:37 means a lot of potassium concentration but lot of positive charge two on the
51:42 side K plus starts flowing its concentration that's driving to flow to the opposite
51:49 through this open potassium channel. this concentration doesn't equal out on both
51:58 because as potassium ion starts leading the and accumulating on the outside of the
52:06 membrane, the positive charge of already potassium will start turning away more potassium
52:15 that it will never reach equal molar of both sides because this positive charge
52:22 start repelling its own positively charged Which is basically the moment at which
52:33 difference at the plasma membrane is diffusion forces which is concentration forces and electrical
52:43 are equal to each other. The will forces still have more concentration of
52:49 saying go go to the other go, but the electrical charge selling
52:56 I have too much of positive I put resistance to you and at
53:02 point the two forces are equal to other. They're opposite in direction to
53:07 other. That's the equilibrium potential and that point there is no net
53:14 meaning there is no more potassium flexing the right or to the left.
53:18 may still be flexing through open channels that's normal biology and thermodynamics but there
53:23 gonna be net ionic movement toward one or the other side because it is
53:29 this equilibrium potential. So these are potentials have values for all of the
53:36 of interest for us. The other that's really interesting is that each equilibrium
53:43 will have its own value and its force. What we call driving force
53:49 that ion will depend on its equilibrium and also the difference between that equilibrium
53:57 and the membrane potential overall. So on with that thought. The explanation
54:01 coming in the next two slides, there are any concentrations are known,
54:09 can calculate the equilibrium potentials. An with potassium is not unique to
54:16 This is just replay the same with . A lot of sodium on the
54:21 . Oh there's a lot of potassium the inside. There's a lot of
54:25 florida on the outside, there's a of sodium on the outside have this
54:29 charged on the podium can across the , sodium starts going through the channel
54:36 also never reaches the equal model The size here again indicates the concentration
54:43 the charge here indicates the charge build . Okay, so it's the same
54:49 . That is the moment where you the equilibrium potential or so do I
54:56 also use this term reversal potential or potential interchangeably. And you'll also understand
55:04 I use that term uh because of training in part but also because of
55:09 biology. So you have uneven distribution charge and each one of these ions
55:16 a certain concentration. So you have little bit of the potassium on the
55:21 of the cell. And a lot the potassium on the inside of the
55:25 , you actually have 20 times more on the inside of the cell than
55:29 outside. That's the ratio. And potassium equilibrium potential value. Noticed that
55:37 C, which is physiological temperature. this is an important term in calculating
55:43 equilibrium potential temperature term. It's minus million volts. Is the reversal or
55:50 potential for potassium, sodium on the hand, is abundant on the outside
55:56 the south, there's a lot less on the inside of the south.
56:00 there's 10 times more sodium on the than the inside. And sodium equilibrium
56:07 is positive 62 million volts. It's positive 55 million bolts and some books
56:12 positive 52 metal bolts and other But it's way way up different
56:18 higher value. And you'll understand why calcium very little on the outside.
56:27 , a lot of it on the , a lot of calcium on the
56:31 , very little calcium on the inside the inside. You can't have a
56:36 of free side of solid floating calcium as I mentioned, it's not only
56:40 secondary, it's not only an it's also secondary messenger. So you
56:47 much control the amount of calcium. it also shows you that there's 10,000
56:53 more calcium on the outside of the than the inside of the cell.
56:57 as far as the concentration gradient calcium is the big big winner
57:04 And the disparity of the concentration of on the outside versus the inside.
57:11 is also abundant on the outside of south about 11 10 times more.
57:17 on the inside of the south and that calc has positive also equilibrium potential
57:24 chloride has a negative equilibrium potential. chlorides negative equilibrium potential is somewhat close
57:30 the resting membrane potential overall which we discuss in the next couple of
57:35 So let me see if I can through this quickly here. Last thing
57:39 I want to say here is the . If you recall A D.
57:44 . And A K palms they work concentration gradients always in the same
57:50 And they use energy 80 P. you chew up the energy. So
57:54 lot of the energy demand in the is to keep up those pumps going
57:58 keeping the homeostasis and keeping the resting potential to its values of approximately negative
58:06 negative 70 million balls. So how calculate the norms potential. And on
58:12 exam you will not need a calculator the exam. You will need to
58:19 the important terms in this equation No ernst equation and important differences in
58:27 concentrations of ions on the outside versus inside. You can remember it by
58:32 molar concentrations 5 to 1 50 or can remember it by ratios is 10
58:38 more sodium. 15 times more of and so on. So to calculate
58:44 earth equation. You have E I this is what we're calculating equilibrium forgiven
58:51 which is in the equation. 2.303 key over Zf cons log of ion
58:59 on the outside of the south Ion concentration on the inside of the
59:04 . R is the gas constant. . Is the absolute temperature. That's
59:08 I said that temperature is an important for calculation of the equilibrium potential.
59:15 is the charge of the ion. surveillance of the ion F is the
59:20 day Sir electrical constant log is based algorithm. So remember that equilibrium is
59:30 balance of two influences diffusion or which puts us an on balance concentration
59:36 electricity which causes an ion to be to opposite charges and repelled by the
59:42 by life charges, increasing thermal energy each particle, increases diffusion and will
59:49 increase the potential difference achieved at Thus, equilibrium of ion is proportional
59:56 T. Temperature. E r T is constant. Therefore uh on the
60:07 hand, increasing the electrical charge of particle will decrease the potential difference needed
60:13 balance diffusion. The increase of electrical . The difference so Z if Z
60:23 two then you're decreasing. Therefore e is inversely proportional to the charge of
60:30 of the ion. We need not worry about our enough in the first
60:35 because their constant the body temperature is . I said that fluctuates too.
60:40 have fever. You know if it's and four F, that's 42
60:47 43 Celsius, that's danger zone. zone that zone. Um So body
60:54 and this equation for these important. let me walk you through this
60:58 So for potassium ion, what we is first of all this term here
61:06 . R. T. Temperature 37 constant third a constant Z. Take
61:15 valence for potassium ions. It all into 61.54 and the term is Mila
61:24 . So all of that can basically our TCF into 61.5 million bells log
61:34 . Based on log potassium on the O. is for the outside of
61:39 cell versus potassium on the inside Of the south. And so for
61:48 , you plug in our T. . Same for R. T.
61:55 as uh And the difference big difference the concentration of the sodium is much
62:05 on the outside versus the inside. is what's gonna be distinguishing the positive
62:11 negative equilibrium potential values chloride. Same here. The same collapse 61 5423
62:19 three are TCF except dizzy is negative is negative, giving us -61.54.
62:29 follows this. Huh? Here we in council calcium doesn't give us 61
62:38 because as we collapse this into the of all these term we're having Z
62:45 plus we're dividing it in half. so you get actually half of that
62:51 in positive terms. So the ions as you can see they will have
63:03 their own equilibrium potential. That is much determined by the valence and very
63:10 determined by the charge positive versus And the concentration outside versus inside.
63:18 we continue with this formula we said there is 20 times more potassium on
63:23 inside versus the outside. That's where get 1/20 or you can plug in
63:30 over over 100 Or 1/21. Doing calculation again, you will not have
63:38 do it but you have to know values in these terms. So 1/20
63:43 of 1/20 is negative. 1.3. you take this portion here which is
63:51 1.3 and multiply by 61.54. And have the calculation of the equilibrium potential
63:59 potassium right? And you can run the same thing for sodium. And
64:07 you run for the same thing for now, N. A. On
64:11 outside, you can plug in A. On the outside is 1
64:17 on the inside is 15. Or can use the ratio of 10 to
64:23 . Right. And what you will is that the value for sodium equilibrium
64:31 now is positive 62 million girls. by knowing, you know obviously the
64:37 of the constant temperature was setting at but by knowing the valence changes in
64:44 charge, the valence degree and the outside on the inside of the log
64:50 and scale is what allows us to it to calculate individual equilibrium potentials for
64:57 individual ions. However, and I know, maybe it will answer your
65:03 . However, the member in potential not just one eye on I said
65:08 this membrane possibility it is surrounded by potassium have a lot of it
65:13 a little bit of it here. that means other ions are involved in
65:18 the overall number of potential. Because equilibrium potential for one ion is
65:24 that one ionic species for sodium equilibrium potential for potassium. And the
65:31 for that equilibrium potential for calcium, potential for chlorate equilibrium potential. Individual
65:38 membrane potential is determined by interactions of ions and mostly by sodium and
65:48 And if you want to you can to this equation also chloride but you
65:53 see much difference when you're calculating the and potential in this case using the
65:58 equation golden equation is pretty much the as this abbreviation here. 2303
66:07 T. Z. F. You have the log base, you still
66:13 the concentrations of potassium on the outside potassium on the inside. The difference
66:21 is that instead of calculating it for ion, you're taking into account concentration
66:28 of another island sodium and outside versus . And the other key term here
66:36 P. K. In this case not like a P. K.
66:39 values permeability. How permeable is the membrane to potassium versus sodium. You
66:49 in the next lecture that at the of the action potential, plasma membrane
66:54 mostly permeable to sodium is dominated by coming in and when the action potential
67:01 going down to resting membrane potential level dominated by potassium leaving the south coming
67:08 of the south. So the permeability change however, addressing member and potential
67:16 membrane potential is dominated and most permeable potassium. This is the T.
67:25 . Value. 40 times more permeable potassium versus sodium. And why is
67:34 ? Because this is just what's happening neurons, neurons have potassium channels and
67:41 channels are leaky and potassium is you see oozing out slowly of the neurons
67:49 potassium channels at wrestling member and These are the most permeable channels and
67:55 have a lot of potassium inside the . Therefore it's very much dominated by
68:03 membrane and equilibrium potential. This resting potential is much closer in value to
68:13 negative 80 value potassium equilibrium potential and 62 value of sodium delivering potential.
68:20 in general in order to derive the Patan trow which is B.
68:27 You have to incorporate at least sodium potassium and you can if you want
68:31 chloride and you have to include the ratios of permeability values for each individual
68:40 . And those p values will change the member and fluctuates and it receives
68:45 and negative inputs. There's p values values where different islands will change and
68:51 will also change dependent on the channel and specific structure that these channels
69:00 So I believe I was actually gonna here today and maybe take one more
69:08 and I want to save this Um So one more question. And
69:15 if you guys have any questions, questions come up after after class ability
69:25 the ability will be influenced by the of the channel and the Connecticut.
69:31 channel, no leaky channels are not same as voltage gated channels, which
69:41 learn about next election. So hang to these questions are great questions.
69:47 are voltage gated channels. We'll talk them about them. Uh As I
69:54 , the flux defiance is dependent on voltage and charge across. But hang
70:00 to that question. That's a great for next lecture because we'll talk about
70:03 compassion and how they play into the potential And the kinetics of those
70:08 Alright, thank you very much. questions today. Really appreciate it.
70:14 had a quick question about the cost exams. Are they going to be
70:18 in person at the casa buildings? that what you talked about in
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