© Distribution of this video is restricted by its owner
Transcript ×
Auto highlight
Font-size
00:00 All right, So this is lecture . Okay, this is lecture

00:07 And what you're looking at on the is actually lecture four. And what

00:12 showing to you is that I've actually all of your videos from Blackboard into

00:23 video points. So to go toe into video points you go Thio video

00:31 dot u h dot eu and you your cougar net. I d to

00:36 in. You can see in the hand corner. Here is my cooler

00:41 . Uh, I'm logged down and have the lecturers. Now you have

00:47 lectures here. 23 and four missing because it seems to be corrupt.

00:53 I'm still working and trying to recoup Number one lecture, the very first

01:00 . If I cannot, we may something where I will substitute that

01:06 Then with the lecture from the other with the first lecture so that you

01:12 it if I cannot recruit the number . But now, if you click

01:17 any of these 23 and four, new window opens and that new window

01:25 the is the video and you can the video. You can scroll through

01:30 . It's very friendly format. You remind yourself what you talked about.

01:36 lecture. We went over neuron zahn different neurons look like. And we

01:45 about important things of classifying neurons. we said that to classify neurons

01:52 you need to know several things. there's several things are the morphology of

02:00 cells the location of these cells. so much they're done rights and their

02:05 with us within specific regions and, , whether they're excited, her inhibitors

02:13 what neurotransmitters to release. We talked the fact that the diversity in this

02:18 in the hippocampus and many central nervous circuits, including the cerebral cortex,

02:24 complexity of the cell subtypes stems from inhibitory cell populations. So in this

02:32 we talked about 21 different subtypes of cells and, uh, only really

02:39 subtypes of excited Torrey self shown here blue green colors, we discussed that

02:46 tourists, also the production cells. means that they connect to other distal

02:51 within hippocampus or exit out of the connecting that structure. Thio other brain

02:57 on the distinguishing factor between these south expression off Cal venden CB while you

03:06 only two really different types of these story parameter all cells the same time

03:14 , flanked in this circuit by 21 subtypes of inhibitory cells and there's inhibitory

03:21 have there's almost located in different The yellow triangles represent synapses. They

03:27 their synapses along Different, uh so dendritic access of these excited terry

03:35 But for the most, their control maintained here, local in the

03:39 Some of them like, for basket cell number two and number four

03:43 very similar. And don't distinguish between is Thio essentially have intracellular marker that

03:52 mark the South sports. So one these baskets cells number two expresses prevailed

03:56 in, and Number four expresses a subset of molecule CCK, which is

04:01 cystic island and equal three. The home message and for the test is

04:05 diversity of these cells and how you definitively tell which subtype of the cell

04:11 looking at. So we discuss experiments which you can visualize neurons and brain

04:18 using infrared differential contrast microscopy. And we talked about is what's portrayed here

04:26 to cells and the two cells. being penetrated by Micro Elektra's, the

04:33 micro electrodes, thes glass, micro contained solution, and you can pass

04:38 current. You can change electrical charge plasma membrane, and you can stimulate

04:43 cells, and as you stimulate the , you can give them the same

04:48 , and you will get a different . And this response is the frequency

04:52 the shapes of the action potentials. the recording, you fill these cells

04:57 you could reconstruct the dendrites and the of these cells. Accents are shown

05:02 and widen them. Rides in Black on the left is an inhibitory

05:07 It's the cell on the right is exciting story parameter, also that we

05:11 discussing and the acts on actually comes of the plane of you leaving out

05:15 the hippocampal structures on its way somewhere outside of the field of view.

05:21 finally we cross stained these cells with markers for some out of Staten some

05:26 provide women and B stands for neuro , which is a stain that during

05:32 recordings you inject the south with the through the electrons through the solution and

05:37 electorates, and you recover their full, full morphology. Then you

05:40 a double stained with fluorescence, markers to recover the internal,

05:48 molecular chemical composition of these cells to sure that you identify that Number

05:54 number four, number six or number 21 subtype of the inhibitory sal that

05:59 particularly interested in. So we then on and talked a lot about

06:07 And as we talked about glia, , we discussed several things. But

06:16 , I'm gonna pause the recording a bit and go and a if,

06:24 you recall we talked about different glial And so we talked about astrocytes,

06:32 dander, size micro glial cells. we also mentioned the band normal cells

06:37 fluid, potent, potentially stump. , like legal cells that provide this

06:44 that separates the interstitial fluids of It's around actual cells from the cerebrospinal

06:51 that are in your ventricles. And we talked about a mile and we

06:57 about Meilin Nation dysfunctions and we discussed , uh, disorders one of them

07:05 sclerosis which affect central nervous system. we discuss it d myelin nation off

07:16 neurons can lead Thio really severe not just physical symptoms, but also

07:24 , because de Milo, nation of that connect complex networks in the brain

07:29 involved in many different complex functions not movements of hands and legs, but

07:34 and thinking and memory and such. also discussed Shark Got Married to

07:41 and that was a peripheral mile and dysfunction PMP 22 over expression of that

07:49 , which led Thio improper Violin Nation from nerves and proper contraction of muscles

07:59 disfigurement of joints and bones during the . So we distinguish the fact that

08:06 multiple sclerosis is an autoimmune disorder, we view these disorders now. You

08:12 have a list again off several disorders we have already discussed during the

08:18 and we will be adding more information these disorders, such as Alzheimer's

08:23 or will come back and talk some about multiple sclerosis. Or we'll come

08:28 and talk about coded and how it the brain, or how any other

08:35 time that we spent on the neurological . So in your folder, what

08:43 have also, and I'm gonna switch tabs now in your folder for the

08:51 content. I think I showed it your last time. You have supporting

08:57 lecture documents, and under these supporting lecture documents, you will be ableto

09:05 movies and some of these movies that mentioned last time. I'm gonna make

09:13 that you can see it this So what is shown in this

09:18 And if I could just get some confirming that you're seeing the movie See

09:25 ? Yeah. Can't see the chat some reason because, yes, we

09:41 see them. And now you can't it because I switched it off.

09:45 All right, so what we're seeing is ah, radial glial cells.

09:49 you see this line going across Za radial glial cell is this line

09:56 the slightest It's almost like a And you have a neuron and this

10:01 form cytoplasmic continuity and use this radio cells to climb its way after its

10:08 location in the circuit, in the in the brain and start communicating with

10:14 their own. So during early you have formation of neurons only very

10:20 parts of the brain. And then those parts of the brain. Durrance

10:24 quite far distances until they find like discussed, they have to find their

10:29 , their city, their neighborhood and their mailbox. And finally there their

10:36 or an apartment or or anything like . So this is how radial glial

10:42 will help guide neuron Is thio their locations? Uh, so in this

10:56 , you can see that it's actually of neurons that are using these complex

11:04 glia light assess of form side new continuity and use them thio essentially a

11:13 stepping ladder as a rope to drag along to find their right address in

11:22 brain. Their precise position in the the middle. Here, this wife

11:28 circle is an injury to the brain . And what you're going to see

11:33 Aziz. This injury happens. You first see micro glial cells in this

11:40 , reached their processes, stored the of the injury and then slowly start

11:46 physically, not just their processes, their cell must forward the side of

11:51 injury. So this is the and now you can see that all

11:54 the processes this is time lapse. the matter of one or two

12:00 you have a movement of Michael Glia terms off micro meters across the brain

12:08 first started from their processes, and you see advancement of actual Selma's So

12:15 Glial cells will be called in when is an injury. When there's a

12:19 Thio to repair and Michael Glial cells involved in sites of kind release and

12:25 of kind regulations. So these air inflammatory molecules and when you have a

12:33 release, a normal level of pro molecules, that's, uh, just

12:38 normal response of the brain to call on the immune response to call up

12:44 the repair response. But if you abnormal cytokine release, then you can

12:51 uncontrolled inflammation on controlled sponsor of inflammation the brain. And you could have

12:58 to glia micro glee as well as size that we refer Thio Leo

13:03 So there's, uh, Rio system . Now the other thing that we

13:09 important and is you hear about glial cancers on DSO glioblastoma, as are

13:20 common, assess brain cancers, eso proliferation of glial cells, scarring of

13:30 cells and uncle Logical activity in glial can can contribute to all of these

13:38 that could go all right, and don't just affect Leah. They affect

13:43 neuron star, located in the regions are surrounding that air surrounded and supported

13:49 basically, who's synapses are controlled by . The um, migration is controlled

13:59 glia. Synaptic transmission is controlled by , so there's a lot of different

14:08 in the brain to which Leah contribute . This is not a passive support

14:16 . This is a very active system is much needed for normal brain

14:26 The blood brain barrier. It's as you can see. First of

14:33 , you have endothelial cells that form walls of the blood. Vessels that

14:39 separated are linked by tight junctions that a lot of a nutrients and a

14:48 of things that cannot pass through tight . They're surrounded by parasites. Parasites

14:54 then surrounded by Astra glial processes, these air the processes from Astra sides

15:02 place themselves around the blood vessels, they're some of the last post the

15:07 control post for the goods passing in the blood into the brain. So

15:13 brain barrier. There's a lot of that we adjust into the bloodstream that

15:17 get into the brain on. There's lot of things that we ingest.

15:22 can easily get into the blood and into the brain the blood brain barrier

15:27 have to discuss within the context off pharmacological drug development or neuro drug development

15:34 general. Think about a neuro drug is a good neuro drug. It's

15:39 one that passes through the blood brain easily. Why would you worry about

15:44 ? Well, because you don't really euro drugs inside the brain. You

15:49 don't inject drugs into the brain apart oh, Botox, she can inject

15:58 treat migraines. You can inject into parts of the nerves and the brains

16:04 So but so what do we do drugs? We take pills, you

16:09 a pill. And what happens to pillow go straight into the brain right

16:15 from your tongue. It just jumps enters into the brain. That doesn't

16:20 . You swallow the pill. What to the pill goes into the

16:24 Gastric juices, acid starts melting and , and part of it goes into

16:31 digestive system they're part of it gets into the blood. The justice system

16:37 all the way down here, So part of it gets absorbed into

16:40 bloodstream, Then it gets carried through bloodstream. And if it passes through

16:45 blood brain very easily, then a of that drug concentration while,

16:51 penetrate into the brain and having And so quite often you see people

17:01 themselves with neurological drugs or even, example, opiates from pain and having

17:07 completely different side effects. So you're a pill to treat neuropathic pain or

17:16 taking a drug to treat epileptic But the side effects all of a

17:23 are that you have massive constipation. is that? Well, that's because

17:29 drug you're swallowing that drug has a effect. If you're targeting opiate

17:36 if you're targeting Europe attic pain, have to know that with opiate

17:42 we also have ah a a We have a covert 19 pandemic.

17:50 haven't opiate epidemic, and the reason is because we have tens of thousands

17:56 people in this country dying every year opioids overdoses from pharmaceutical opiate overdoses because

18:06 effect of those for opiate is very . Few milligrams and the deadly dose

18:11 opiates is just a few times of does just multiply that few milligrams by

18:18 or five times, and you reach deadly dose and opiate receptors so located

18:23 the brainstem regions that affect vital functions as breathing such as heart trade.

18:30 so, as you're treating the pain of the, uh, opiate addiction

18:35 because it makes you feel good to just takes away the pain, but

18:41 causes massive constipation. That's a systemic as a systemic effect, and them

18:47 treated by another pharmaceutical drug that is designed to treat constipation created by

18:57 Okay, so we have a neuro . Let's say you're treating some

19:03 You're treating some pain. You're treating or or you're treating another disease that

19:08 talking about you're treating, and you massive constipation. Now you need a

19:13 to treat constipation, and that's because that you swallow will have a systemic

19:18 fact if that drug is not effectively through the blood brain barrier, that

19:24 you have to swallow Maura Maura of drug systemically in order for a fraction

19:28 that to pass into the brain toe in fact, so then, you

19:33 , obviously, FDA that safety and studies to make sure that drugs are

19:38 and notifications. But we do have a problem with a lot of drugs

19:42 are safe and applications that are being off the market. Or, like

19:45 mentioned that have very close. The dose is very close to the lethal

19:54 , which makes it very difficult for , especially dozing themselves. Thio avoid

20:01 overdoses on potential mortality, so huge and most neuro pharmacological drugs and have

20:09 take the blood brain barrier into How much of the drug? How

20:14 is it? How well is it into blood brain barrier? And we're

20:20 from nature as well. I think learning from nature. We're going back

20:25 and more so from nature. We're more plant derived medicines, but we

20:30 have to keep in mind that anything we see pharmacological pharmaceutical synthetic usually comes

20:36 a plant derived experience from applying derived that later is being synthesized and So

20:44 think there is slight shift in the drug development or natural plant derived molecules

20:51 than synthetic molecules. Or, if synthetic, maybe that their bio synthetic

20:56 synthesized by either biological, um players as the yeast, for example.

21:07 , so we have this wonderful world glia, and all of the glee

21:11 served different functions that we discussed. today we're moving on to talk about

21:16 member and oppress or resting member in so neuronal number in a trust.

21:23 what is that? It's the fact if you have this recording here set

21:31 , you have this micro electrode and have the ground and the ground is

21:38 zero zero volts. Zero millet Relevant scale for measures off Electrical activity

21:47 neurons is on the order of millet . So if you say that the

21:52 or the outside of the cell is and you have ah amplifier connected to

21:56 volt meter, and you sink this across plasma membrane into plasma membrane,

22:03 volt meter will show immediately, minus miles 55 minus 70 minus 75.

22:10 this is arresting member and potential of cell. This is the number of

22:14 that is created by unequal separation of , with a negative charge is gathered

22:20 the side of Plas Mick inside off cells and the positive charges gathered on

22:27 outside off neuronal membranes. Um, this charge again in, in in

22:35 test this is not to confuse, know? So what is the resting

22:38 and potential? Exactly? Is it 60 or did you say it's minus

22:43 or 65? Or is it minus ? I minus 75. So the

22:47 is that different cell subtypes will have variation in this memory of potential,

22:52 approximately it's about minus 60 to about 70 minus 75 million ball glial cells

23:00 a much lower arresting member and potential minus 90 million balls. What you

23:06 on the right is you have on right and illustration, and we discussed

23:11 the first action potential that was recorded Hodgkin and Huxley. And the action

23:17 the action potential all occurs at the . When you're looking at this membrane

23:22 on the bottom left and you're seeing , blue negative charge and red positive

23:29 . If you insert channels and this discharge very quickly will reshuffle of the

23:35 conditions so the cells receive enough of synaptic input on their down rides.

23:41 of the excited Terry input in the input does not quenched excited for

23:45 But that means to sell Selma's. going to get deep, polarize us

23:49 . Deep polarized. It will produce action potential that the acts on initial

23:54 and the acts on Hillock, which located, ride at the base of

23:58 pyramid here, where the accent is out of the base of the pyramid

24:03 this very fast fluctuation from about minus minus 60 million balls plus 40 million

24:10 and then returning back thio minus 70 back to the resting membrane potential.

24:16 blip is only +123 milliseconds in It's a very, very fast action

24:22 . So the reshuffling of the car first positive car and going in and

24:26 polarizing the south and then positive card leaving is re polarizing the cells,

24:34 we'll discuss the action potential number and in greater detail in the next couple

24:42 lectures. But the reason why oppressed have the separation of charge. That

24:49 poised to react very quickly quickly is we need very quick reactions we need

24:57 neuron is to produce on to react the environment and some of the things

25:05 we do and neurons produce action potentials reflexive, and they're very fast.

25:12 it would be a pity, right you step on the nail, and

25:16 of a sudden you had to contemplate a few minutes whether it's really hurting

25:22 . Whether it's hurting you a you wonder what kind of nail it

25:26 , whether it's rusty nail whether you put your leg and pull you like

25:30 not even going to do that, going to react before you know

25:34 If you step on something sharp and , if you put your hand on

25:39 hard for super cold, you will it immediately. Then you'll think about

25:44 , and even that after some time will feel the pain, then maybe

25:48 itch, but not at the very . So this reflects of behavior is

25:54 where eyes were actual potential, so very fast and where you can have

26:00 of this reflexive behavior that is mediated by a single synapse. So we're

26:06 discuss now this within within the context the knee jerk stretch or patellar tendon

26:18 . Okay, it's it's It's the thing Knee jerk or stretch reflects or

26:23 tendon reflex. So you have this tendon here, and this is a

26:28 arch. It's the simplest kind of badly that we're discussing When you goto

26:35 doctors office for a yearly check up to a neurologist office. What they

26:40 do is they will sit you down they will take a soft knowledge and

26:45 will top on this patellar attendant on knee tendon here. And the response

26:53 that your lower leg, the lower of your leg, is going toe

26:59 up without even thinking. So this it is a stimulus stimulus. You're

27:10 the patella tendon and at the same , also stimulating the muscle spindle off

27:16 quadriceps muscle, which is an extensive . This extensive muscle has the nerve

27:22 from the dorsal root ganglion, sensory . So here what you have to

27:28 is here, I would advise to , as I said at the beginning

27:32 the semester that you should have a for for neurological disorders that you should

27:41 have a table that does something like . That place is sensory cells,

27:59 cells into neurons. And what's the type of cell that you studied,

28:03 criminal cell drama All cells. And should know as much as you can

28:10 these four sub types of cells Rahman sensory motor and into neurons. Sensory

28:19 in here are after parents. So current information from the periphery, from

28:25 muscle spindle activated muscle spindles, some stimulus on the attendant informs that sensory

28:33 , which is a dorsal root ganglion , and that sensory neuron through his

28:39 Axiron will inform the some of the neuron and through Central Act song will

28:47 activate another red neuron, which is motor neuron. So once the sensory

28:54 root ganglion neuron is activated, it release glutamate in the spinal cord

29:01 and it will release glutamate on the on the Denver writes off the multipolar

29:07 neuron cell, which is shown an and that motor neuron cell is an

29:13 Farron going away from the central nervous into the periphery. And the E

29:20 is the motor neuron. The affair are the sensory neurons, dorsal root

29:28 cells to get excited by enough of tapping on the need. They released

29:33 on the modern neuron. These air uniforms ourselves to sensory neurons. The

29:39 neurons are multipolar ourselves, and modern will then releases the title Colleen onto

29:47 muscle cells. So when I said you should outline what these cells

29:51 you can put the censoring around the Unipol, her anatomy. It is

29:57 during your arm. It releases Motor neuron is multipolar anatomy,

30:07 When when? When motor neuron is , it's and it's an e

30:12 Dorsal root ganglion or sensory is an . In this is an E

30:16 When motor neuron is excited, it . That's called Colleen. Okay,

30:23 you put the receptor the neurotransmitters underneath cell that they release. And just

30:30 activating a single synapse here between sensory and motor neuron, you're now telling

30:36 quadriceps extensive muscle to contract. This an illustration where the single synapse and

30:43 are very powerful synapse. Actually, off one motor neuron means a twitch

30:49 a muscle where you activate one motor through a single synapse from dorsal root

30:55 , sensory neuron, and you have contraction of the quadriceps muscle.

31:01 we know that if you just do , the movement off the leg is

31:07 going to be very efficient. And reason for it is because you haven't

31:14 hamstring flexor muscle. And for Thio, extend and contract extensive

31:21 You have to relax the flexor So how do you do that?

31:27 the same dorsal root ganglia and sensory . That same afternoon neuron will carry

31:33 to the motor neuron that contacts extends muscle. But it will also contact

31:39 Interneuron, which are living in the cord proper. And these inhibitor into

31:45 will release glycerine. So unlike the into neurons that live in the cerebral

31:53 , in the in the brain, spinal cord Interneuron released lysine, the

32:00 N s inhibitory Interneuron. They released Obama Immuno beauty, Eric Asset.

32:08 , so once glycerine gets released is a different neurotransmitter that is well expressed

32:14 the inhibitor into neurons in the spinal . Once glycerin is released, this

32:20 neuron that is targeting the flexor hamstring is inhibited. Inhibition of this nerve

32:28 for the flexor muscle to relax while extensive muscle properly contracts and you have

32:36 proper movement of the leg upwards. what? What what? What do

32:44 what? There's a lot of things you can start thinking about now.

32:48 of all, you have a monos IQ reflex here. What is the

32:52 in app Pick, that means one involved spinal sensory neurons, the spinal

32:57 motor neuron to contraction of extensive muscle reality, even for the archery

33:02 To be successful, you have to opposing muscles, so it does involve

33:08 than just one set up. The thing is that you have to think

33:12 because the inhibition of the opposing muscle the flexor muscle happens through additional

33:20 Through the inhibitory Interneuron, there's gonna a slide funeral, second delay when

33:27 muscle is completely relaxed. In other , the extensive will start contracting

33:32 and then this is going to fully along for the leg to move

33:37 So it's fall of synaptic for this to be effective, fully effective,

33:45 have to involve more than one And what There are many reflexes in

33:50 body that involve different parts of the . Actually, there are complex

33:54 That's one example is a gag reflex gagging or vomiting reflex, which involves

34:02 of the brain stem, involves, , brain stem nerves and brainstem structures

34:10 cranial nerves. So it za lot complex but understanding with circuit, knowing

34:16 three subtypes of salsa choosing here. Unipol, a sensory African releases

34:22 multipolar, excited Terry and motor neuron at the top. Polian Multipolar inhibitory

34:29 of the spinal cord releases glycerine. , so these 33 candidates here,

34:35 should know really, really well. imagine a situation. You walk in

34:40 doctor's office or neurologist office. They're doing a regular check up, and

34:45 taps on the leg and the leg move, so he has to tap

34:50 the light harder. He sees the moving, and then it's going back

34:55 away, just moving a little, not moving enough that it requires.

35:01 it requires a lot off stimulus. you are now in the field and

35:11 have to pretend your doctor What is hypothesis? Anybody can chime in or

35:20 their hand. What would you say wrong in the circuit? If you

35:25 thio, give such strong stimulus and just seeing a little bit of

35:32 Anybody you can take a Gus, don't know. I'm just looking at

35:40 SAARC it. Why does it need lot off input? Maybe the censoring

35:46 own is not working well enough, it seems to be starting to move

35:52 legs. So it's it's carrying the , right? That's starting to move

35:58 lag. But then it doesn't What's what's going on? Maybe the

36:02 is decreased. So if you decrease , what happens if you take?

36:09 if there's no inhibition off the flexor , what happens? Can quadra such

36:16 efficiently and move the leg? Now start moving the leg and will stop

36:21 you can say, Well, so there are other tests and neurologists

36:26 , uh, general practitioner so much and me on these kind of observations

36:33 by testing, you know, the of the eye. Whether you trace

36:36 eyes, whether you can focus in odd whether your hotel attendant is

36:41 All of these things are starting to people if there is some dysfunctions.

36:46 a sort of a rudimentary, crude of testing at the system. Of

36:51 , then you'd have to go through casts and look for, um,

36:56 , um, nor sophisticated testing his potential around out. No, it's

37:05 It's a good way of saying actual that's run out, and it actually

37:10 potentials run away to e. Guess you're saying is, uh, then

37:17 would say no, it's a little . Maybe what you're thinking is something

37:22 tetanus. So when the muscle is active, active, active and kind

37:26 a locks up goes flaccid from too activity, a piece are all or

37:33 . If it goes, it goes . Yes, but yes. But

37:40 if you have a dysfunction at the off the motor neuron receptors?

37:46 if the glutamate receptors are not functioning so yes, you're correct. If

37:50 activated, you produce an action You're seeing a movement. There is

37:54 action potential that happens in place. a matter of fact, with

37:57 There is neural transmission. It's a of fact. Maybe there is increased

38:02 or sensitivity off inhibitory circuits. Maybe is desensitization of sensory neuron to so

38:10 the stimulus needs to be much stronger orderto initiate that action potential. Great

38:16 , Arts Mhm. All right, no, these cells know what they

38:23 that currency parents neurotransmitters to release and know that parameter will sell. This

38:28 excited to resell on the C. s and they have a campus and

38:32 cortex that we discussed and know the into neurons in the cortex. Also

38:37 they were released gabba and they're also and come in different shapes. So

38:43 go back and talk about some basic . Maybe it's basic for some of

38:47 and hopefully not through basic. But have water were made up of

38:52 Our brains are made up of water our brain styles air floating in this

38:58 well, they're not floating. Some them can move micro glial cells,

39:02 they are in this acquis environment. , uh, water oxygen attracts extra

39:09 and has negative charge. Hydrogen has positive charge the hell biker Vaillant bombs

39:16 other Poland molecules dissolved in water. I on such as chloride,

39:21 potassium, calcium dissolve, are surrounded waters and a lot of fans,

39:27 also call these clouds of hydration, clouds of waters of hydration that that

39:33 attracted by the charge of these ions surround the ions, my aunts,

39:42 and molecules that having that electrical charge ions form ionic bonds, such as

39:48 Seoul, sodium chloride. Difference in number of protons and electrons is if

39:53 ionic balance. You're charged. You Mondale and ions and die. They

39:58 Somalia. Vaillant Um, cat It's positive and a plus. Die

40:06 Catan is positive. Calcium two plus I m is negative. Ion chloride

40:14 one plasma membrane we already discussed is of all, it's a possible IPIC

40:20 air. But more importantly, we about the fact that it's a possible

40:25 bile air that is dynamic, So have the movement off the proteins inside

40:32 foster lipid bi lair. You equally have the movement off ions across plasma

40:41 . So the most important ions that discussing as they relate to the resting

40:46 of potential of sodium and the Potassium K plus chloride and calcium.

40:52 plots. You can see that there unequal distribution of these islands across plasma

41:01 in parenthesis. Here you have the of these ions that are measured in

41:07 Mueller. So there's 18 million Mueller on the side of plastic intracellular

41:13 and there's 145 million Mueller sodium on cellular side potassium. There's 135 million

41:22 on the inside of the cell, inside of the cells are dominated by

41:27 high. On outside, there's only million Mueller potassium. There's a lot

41:34 chloride on the outside, extra cellular and little chloride on the inside of

41:40 south. Only seven million moment for . There's only 0.1 Micro Moeller.

41:47 is an exception. Calcium 0.1 micro on the inside, often neurons and

41:55 million Moeller on the outside. for calcium, actually, there

42:01 ah, highest, uh, this in concentration between the inside and the

42:11 of the South. Um, and very important. There is not that

42:17 calcium that is freely floating inside the . Most of the calcium stored inside

42:21 intracellular calcium stores, such as more two plasmid particular Um, word is

42:27 up by calcium bounding proteins by calcium proteins and other molecules, so calcium

42:37 is a very kindly regulated inside the . But calcium has a very strong

42:43 drive because of the difference in the radiant to be driven inside the south

42:50 calcium. Too much calcium could be dangerous. So that's why calcium intracellular

42:55 controlled. If there's too much calcium the South, you can have calcium

43:00 toxicity or toxic activity in the cells cell death Do thio Abnormal levels of

43:09 eso well, Do you have all these individual channels for sodium,

43:16 Florida and calcium islands You also and Ionic Pump and Ionic Pump.

43:21 these channels that work partly down the ingredient, bionic comp works against

43:29 Great answer. It uses energy. teepee converts it into a D.

43:34 , and it transports sodium from inside outside. Despite the fact that there

43:39 a lot of sodium on the outside the self, and likewise, there's

43:43 lot of potassium on the inside of cell, but the pump will use

43:47 teepee and little transport potassium molecules into inside off the south. Alright,

43:56 remind ourselves about the building. Basic blocks of nature. Those air,

44:03 amino assets that bound get bound up polyta tied bonds, and you have

44:09 central amino acids and non essential amino know that essential amino acids are

44:16 You don't have them, so you to seek them out in nature.

44:20 sources plant in animal sources to provide with these essential amino acids and

44:28 tied bonds structures and allow for the of chains of these amino acids.

44:34 as you create these chains of amino that are bound up by Paula Peptide

44:40 by peptide bonds, you then can them into data sheets. You can

44:45 them into Alfa Helix system from the structure to the secondary structure. The

44:51 a helix is may become a single membrane segment. There's four trans membrane

44:57 shown here in one sub unit, this one membrane sub unit becomes one

45:02 the five. Subunits have come together comprise a trance membrane Rodion Channel.

45:09 it starts out from these building blocks joining bricks together in tow, ropes

45:18 amino acids, twisting them together, folding, putting them into the sub

45:24 , joining the sub units together. , secondary, treasure and Co ordinary

45:29 . One. This is how things Belden these house. And when we

45:35 about ion channels, ion channels are selective. So we said that there

45:41 a sodium channel that there's a potassium , that there's a calcium channel.

45:47 look here on the right. This a sodium channel. Sodium channel is

45:55 permeable or sodium. So these channels the inner luminous the inner most parts

46:02 these channels that they're highlighted here. limit of the channels they are

46:08 the function of like molecular seething because not just a chemical Grady int,

46:16 its chemical interactions and electrical interactions that within the loom in itself. The

46:22 what ions pass through this channel when comes in from the outside up the

46:31 from the extra cellular space again it's by water. That water is the

46:38 molecules traveling into more narrow part of channel. These waters to increasingly more

46:43 stripped. And there is a very microsecond interaction between sodium and the amino

46:54 residue, negatively charged amino acid residues are located in this normal, enormous

47:00 of the channel. And by this interaction, there is a propulsion of

47:06 sodium, again guided in part by diffusion all forces into the inside off

47:12 cell, where, on the inside of the channel again sodium, gets

47:17 by water and gets propelled onto the of flies. Mick side of the

47:24 . So if you look at the muscular junction, that's a tall Colin

47:30 junctions between neurons and muscle between motor and muscle, where you have release

47:36 That's a title Colleen single acetylcholine receptor can conduct AH 100 million ions a

47:45 . I stands for current. The I R. I sense recurrence of

47:51 lot of charge. A million islands second gets conducted. That's a lot

47:56 charge, as opposed to an a a T P pump on a k

48:01 . T P ace, which can deliver 100 ions per second. It's

48:06 slow mom that works against concentration ingredient energy and maintaining this, uh,

48:17 , concentration and balance across plasma numbering sodium and potassium islands. So channels

48:24 selected bionic filters. In this sodium gets stripped off the waters of

48:30 by amino acid residues and enters But if it was a potassium

48:37 it would be larger in diameter and would be trapped and send back

48:43 That should bring an interesting question. that mean that because potassium is larger

48:49 diameter, it would require a larger and therefore smaller down in our

48:55 On such a sodium minds can also through potassium channel, and the answer

49:02 no. There is a lot more it. We're not talking about channels

49:07 are specific to sodium channels that are to potassium. There are protein channels

49:12 glutamate receptor protein channels that actually passed , potassium and calcium through through its

49:20 lumens. But there's other things that here. Size does matter, but

49:27 is not the only thing, because smaller ions actually have higher attracting

49:34 so they have larger clause of hydration them. So there is another interaction

49:41 , and you have this very specific here with amino acid residue that is

49:47 to sodium channel. And you will this negative amino acid residue in the

49:52 channels Well, but it's different, then the interaction is different. The

49:57 of it is different. You will have a positive amino acid residue for

50:02 . Channels for negative islands passes so size is important. But

50:10 it's not just that it's molecular. evening. It's electrostatic forces that are

50:17 this, helping the diffusion all forces the aisles across. Alright, so

50:23 law if you remember. If you , you will know E equals

50:31 These voltage that stands for volts and relevant scales for neurons is Mila

50:36 Iet's current is measured in amperes and . Relevant scales are million and Paris

50:46 micro and pears are is resistance, is measured in arms. So the

50:53 the larger the surface area, the the structure of the cell, the

51:00 resistance it has but sells a very and therefore the resistance and neurons is

51:05 in mega homes. You also have , which is the opposite. It's

51:12 inverse of resistance, and it's measured Siemens for us, The relevant scales

51:18 and Nano Seaman's for the conducting of and individual channels. So the equals

51:23 R G is one over are. I is equal GV. Everybody sees

51:32 so arms law will come back to and we'll have Thio use a

51:37 But let's talk about how this diffusion charge happens across plasma number,

51:42 And if you're looking at just the Grady Int, that's very simple.

51:46 have a lot of sodium and Florida the left. You have a plasma

51:49 in the middle. There's no There's no Ionic flow in certain channels

51:54 open the channel. Sodium in Florida slow down its concentration radiant until there's

51:59 amount of sodium in Florida across plasma . So this is just simple concentration

52:07 . But we also know that Ionic is not just influenced by chemistry,

52:13 it's also influenced by electricity and electrical . We know that on voltage drives

52:21 through channels of voltage can repel on can attract, so sodium cat ions

52:28 gonna be attracted to negative charge are be attracted if you're looking at

52:33 um uh, battery, and you imagine that you have a battery across

52:41 membrane and this battery with attract the and the cathode will attract cat

52:48 and the positive and an out will an islands. And the reason you

52:54 have the separation of charge across And that's the reason that gives rise

53:00 difference in electrical potential that you're measuring minus 65 mil of alters. The

53:06 is this. Negative charges accumulated, the inside the end voltage on the

53:12 , minus voltage on the outside. is minus 65. Outside is zero

53:18 your member and potential the membrane or M address. The membrane potential is

53:25 . Thio inside of the cell is the negative on the inside of the

53:30 , which is approximately negative. 65 17 syllables. Remember the basic things

53:37 current flows in the direction of net of positive charge. That means Anna's

53:42 opposite and katanas move same as current . And if you reduce the

53:49 if the inside of the cell becomes negative, less negative charges on the

53:54 you have reduction in charge separation between and outside of the South, which

53:59 called deep polarization But if you accumulate of the negative charge on the inside

54:04 the South, you have an increase separation of charge. There's more negative

54:09 now, and this is called hyper . Now each ion has in a

54:16 , um, potential because each ion not only driven by the,

54:23 chemical radiant but also by the electrical int. So Equilibrium potential or e

54:32 . I also will use it as reversal potential. So I mentioned equilibrium

54:38 , and I also mentioned reversal potential ionic. It's a potential it which

54:45 diffusion. Allfirst's is chemical radiant forces electrical forces to charge are equal on

54:54 to each other in strength. And is no Nana Janek movement across plasma

55:00 . So let's look at what scenario talking about here you have inside of

55:04 cell and you have potassium ions, lot of potassium ions illustrated on the

55:10 by their large K plus, and can see that accumulation of the

55:15 If you have a plasma membrane with channel and you have a potassium

55:21 you will have the flow potassium across channel onto the other side down.

55:27 concentration ingredient where there is little potassium the right small K. Plus,

55:32 have other ions, or you have molecules that are negatively charged on the

55:37 and outside of the cell that cannot . So just, for example,

55:41 charged ions and the proteins and the of the plasma membrane, the cannot

55:47 through the plasma membrane. Not all them. But what happens after some

55:52 ? As potassium flows down his concentration , it actually stops flowing before it

55:59 the same concentration of both sides and from the right side. Why is

56:05 ? Because, as potassium flows to right side, positive charge again,

56:10 that the charge separation and charge accumulation happening across plasma membrane. So if

56:17 look in the diagram on the what you're seeing is a lot of

56:21 charge. On the side of Solich , ah stuck onto the membrane.

56:26 lot of positive charge of extrasolar side onto the membrane, but the inside

56:31 the selling the side of Saul or environment. They're equal, their charge

56:38 . The charge plus and minus are , So the only separation and accumulation

56:43 across the plasma membrane. So as potassium flows across plasma membrane, the

56:49 charge now starts accumulating on the other of the possible number. And guess

56:53 happens that positive charges. A repellent is our repellent to positive ions coming

57:01 that repulsion. That electrical repulsion is electrical force. Now that electrical force

57:07 counter acting the chemical force, it against the chemical Grady and saying,

57:13 , you're not gonna put more I'm already positively charged on the

57:17 I don't care. There is a more potassium will left on the inside

57:20 the cell. Not more of it going out now. The electrical force

57:26 equal in size to the chemical um, driving for us when those

57:31 forces are equal to each other. when you have a number and potential

57:37 a potential at which there is no ionic flow across this channel or across

57:44 membrane or potential behind Um, so is ah, Ionic reversal potential for

57:53 . There's Ionic of Russell potential from , and we can calculate these ionic

57:58 and there is a formula by which calculate. But let's look at this

58:03 number and then small ionic number It's a small amount of concentration.

58:08 can cause large voltage fluctuation. So you have an open channel reshuffling very

58:15 , we shop Lincoln cause you know of tens of millet balls in the

58:20 over milliseconds. Net Ionic differences at membrane number two and that ionic difference

58:27 charge accumulation and charge separations across plasma . If you go on the inside

58:34 the cell is neutral. The Ionic Force What we call the driving force

58:41 actually the difference between the member and on the reversal potential for that specific

58:48 . That means that if member and is very far away from the value

58:54 the reversal potential or for the Librium for ion, it will have a

59:00 driving force. And we'll address that we come back on Tuesday, because

59:04 requires a separate diagram to explain what force really is. Number four.

59:10 Ionic concentrations is known. We can Ionic reversal potentials for each ions that

59:17 is right. So when we come , first of all, we're gonna

59:23 about sodium, and you can see there's nothing different here for potassium,

59:29 is, that is different for The same way of sodium is positive

59:33 the outside and is going to start on the inside of the south

59:37 There's going to be accumulation of positive on the inside of the South,

59:42 with sodium positive violence, despite the that there is still larger chemical concentration

59:47 sodium on the right side, them of himself. Okay, but now

59:51 is no Net Ionic charge, and is the liberal potential facility. A

59:56 Mhm. So we know that we calculate these ionic reversal potentials or ionic

60:04 potentials because we know the concentrations off inside the cells. So when I

60:12 showing you earlier in a 18 and said 18 million Mueller and the inside

60:17 45 on the outside next to there is a cual Israel potential for

60:22 and the liberal potential sodium values. 56. Next in potassium is equilibrium

60:30 for potassium negative 102 chloride negative Calcium equilibrium potential positive. 125.

60:41 is Mila. Val's not in Miller Moeller These air the concentration Grady

60:48 that we talked about the chemical Grady INTs what you have. E

60:53 a E, k E C L E C A r Equilibrium potentials or

60:58 potentials for these individual ions, and table on top right actually illustrates that

61:06 have a huge ratio disparity that we , especially for calcium ions. As

61:15 can see, there's 10,000 times more ions from the outside of the cell

61:19 compared to the inside. It's 20 more potassium on the inside. There's

61:26 times more sodium on the outside, the outside solution off our brain neurons

61:32 sold to sodium fluoride. But this , for example, and other animals

61:40 depends on the environment like squid, have about 400 million molar sodium chloride

61:46 they live in a very salty environment . So our environments and part dictate

61:52 the environments and then are created inside bodies for the South, such as

61:57 cells. So what you have now the stable is you have each

62:05 You have a concentration of that. , on the inside versus outside,

62:09 a approximate ratio of that high on vs inside and you have a

62:15 um, potentials that are measured at temperature 37 degrees south centigrade on.

62:22 can see that they have all very values. So when we,

62:29 come back in the following lecture will look at the nurse equation, we're

62:35 out of time today to go through Ernst equation and for me to explain

62:39 and good enough detail. So we come back and we'll talk about it

62:44 Tuesday. We're not gonna have our office hours today or discussion because we

62:53 don't have much material to review. , I wanted Thio again remind you

63:00 for graduate students, I will send separate email about the meeting next week

63:07 if you have difficulties with Casa, let me know what those difficulties

63:12 Whether you contacted Casa's support and let let me know as soon as you

63:19 , the might be a possibility that will allow you to re log in

63:24 test out the system one more Potentially today. So please send me

63:29 email about that. Please check that can log on to the video

63:34 Uhh video points dot u h dot d u to make sure that you

63:40 access your materials. When you get video points, you'll actually see two

63:45 43 15 63 15. They're two that I'm giving the semester. So

63:52 lectures start with Tuesday Thursday. You'll Tuesday Thursday in front of the lecture

63:58 so that you know you're looking at particular electric. Uh, so you

64:05 the chat Thio, see what we dio or see if you have any

64:18 with cell death due to too much , be do thio over excitation.

64:26 , if there is too much excitability the brain and you will have a

64:33 of calcium activity. But you can imagine one thing is I mentioned to

64:40 that Astra sites will control local rises calcium concentrations. So if those calcium

64:49 air inside the South, cell has deal with it. If the calcium

64:53 outside the cell, which will drive mawr calcium on the inside of the

64:58 , right, then you can think glial dysfunction because glia will should be

65:03 up this extra calcium and siphoning it its network. But if it's not

65:08 so, then it can become even detrimental. To the South, there

65:13 , ah, programmed cell death that get turned on by a callous UMA's

65:19 , calcium excited toxicity. It's called excited toxicity because usually excitation and toxicity

65:28 related to excite hitori cells being Do you have an approximate date and

65:36 ? The rest of the electric videos be applauded. Right now you have

65:40 videos that are already on video So if you are still looking

65:46 Blackboard thistle is old news. You to look at video points. There's

65:53 lectures there. The first lecture I at the beginning off the class is

65:59 . I'm trying to fix it. I cannot fix the first lecture,

66:03 upload the first lecture from the other that I'm teaching this semester on.

66:09 very similar. Maybe some nuances will missed, but it's very similar to

66:15 . So if I cannot rebuild, will upload the other one. After

66:21 , they should be six videos right? Not all. You should

66:27 the syllabus and noticed that this is five. So after today, there

66:35 be five. But if one of is malfunctioning, you will have four

66:42 I can fix number five. I that answers the question. All

66:47 Great. Thanks. Awesome. Thanks being here. Let's try to start

66:55 our videos. I think everybody is , ah, acclimated to being online

67:01 talking online. And don't be Turn on your videos. Next

67:07 At the beginning of the course, don't have toe record. Uh,

67:11 we interact at the beginning of the with each other that z one of

67:17 issues. Thank you for being Have a great weekend on email me

67:22 you have any issues. Otherwise, will see you next Tuesday Day

-
+