| 00:03 | This is a lecture number seven of . And uh these are the slides |
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| 00:12 | the previous lecture. The previous lecture on available for you to view um |
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| 00:24 | U. H. Video points. wanted to quickly address this section here |
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| 00:32 | I expect from you to know. examine the three cell subtypes that are |
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| 00:38 | in this simple reflex. What type south having morphological e what type of |
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| 00:46 | they release where they're located and whether neurotransmitter is inhibitory or excitatory onto the |
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| 00:56 | south. So if you have not up with this that I would strongly |
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| 01:02 | you to do that. Also as review on Wednesday would do the same |
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| 01:09 | if we campell circuit and as far describing the grammatical south based on the |
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| 01:17 | junction functionality and all of the good we discussed in the hippocampal circuit. |
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| 01:24 | some of the things for the member potential are quite basic. Mhm. |
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| 01:31 | I think that the thing that I at the four ion sodium potassium chloride |
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| 01:38 | calcium. The action is happening at level of the numbering. Mhm. |
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| 01:44 | is an unequal distribution of charge across fossil of bi layer ions cannot really |
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| 01:54 | . They have to cross through their ion channels. And you should start |
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| 02:02 | notes on these terms here in You have minimal or concentrations of ions |
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| 02:11 | in the parenthesis for sodium 145 Modeler on the outside About 18 or |
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| 02:20 | other from the inside of the Another value here is E. |
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| 02:27 | A. Which stands for the equilibrium for sodium. And we finished last |
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| 02:35 | you're talking about equilibrium potential arms The equilibrium potential amino acids are you |
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| 02:44 | blocks and those building blocks and building beautiful secondary tertiary ordinary Centenary protein structures |
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| 02:55 | protein channels that are comprised of multiple units whether they're trans membrane or channels |
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| 03:03 | whether they're trans membrane receptors without a inside. It also contains multiple of |
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| 03:10 | subunits and individual ionic channels. When talking specifically now about voltage gated |
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| 03:22 | And for the purposes of the next on action potential dynamics is voltage gated |
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| 03:31 | that we're talking about. That means it's a change in voltage that will |
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| 03:37 | these channels. But before that we went over some of the basics some |
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| 03:43 | of biochemistry and biophysics of the waters hydration and movement. And the vehicle |
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| 03:51 | that ionic channels are selective sibs for specific interactions and sodium channel for sodium |
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| 04:03 | , potassium potassium ions, calcium. there's a variety of these different |
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| 04:09 | and one cell can express up to different subtypes of these channels and because |
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| 04:16 | express these different some types of that's why they have this different dialect |
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| 04:21 | they all speak Arms Law vehicles. let me make sure that I think |
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| 04:30 | some of the slides overlapped and in presentation so make sure that I'm not |
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| 04:42 | myself. We talked about we haven't about this yet how we've gotten to |
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| 04:49 | equilibrium potential insurance potential. Right? let me just there was this oh |
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| 05:03 | goodness ! Hold on a second. . And on his law that we |
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| 05:16 | and what I was mentioning is the scales for neurons. Millet balls, |
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| 05:21 | volts, million pairs mega longs for , PICO and pears, PICO, |
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| 05:30 | . Uh nano c minutes ions will down their concentration gradient. Simple diffusion |
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| 05:41 | the equal out on each side, the concentration gradient. But there's also |
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| 05:47 | battery that forms and this battery forms plasma member and in the battery positive |
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| 05:55 | ions are attracted to cathode because the end of the battery negative and ions |
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| 06:01 | florida attracted to positive of the which is an animal. Uh So |
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| 06:09 | electrical potential, It's not just a gradient, the chemical gradient, but |
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| 06:14 | also the electrical potential that has its electrical force. That will be responsible |
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| 06:21 | creating a certain movement of ions that off across plasma membrane. So, |
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| 06:27 | have separation of charge because ions are positively negative charge across the membrane gives |
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| 06:33 | rise to difference in the electrical The inside versus the outside is what |
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| 06:42 | number of potential is. So then will say, well, what is |
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| 06:46 | outside charge? And the outside charge presumed to be zero, which means |
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| 06:52 | outside Aquarius environment of neurons Is like grounded to zero Millersville value. And |
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| 07:02 | the plasma membrane if you were to one of those electrodes that I was |
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| 07:07 | you. You place inside the south plasma number and you have a difference |
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| 07:12 | negative 65 millennials outside vs. Inside all of the charge is accumulated. |
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| 07:22 | differences accumulated across the two sides of plasma numbering. That's negative 65 million |
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| 07:31 | , negative 70 million bowls, -75 balls. Someone depends on the |
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| 07:39 | someone depends on the structure of the That you're recording from with this resting |
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| 07:46 | of potential value somewhere on -65 -17 balls. And these values are important |
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| 07:54 | we will chart out the reversal potential are equilibrium potential values for each ion |
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| 08:00 | you will be responsible for knowing them the task. Some basic things can |
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| 08:09 | direction of net movement of positive If you increase the charge you have |
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| 08:15 | polarization, that means there's more charge , hyper more polarity. So it |
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| 08:21 | go from -65 to -75 -80 If you reduce charge separation It goes |
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| 08:30 | -65 to -45, your deep polarizing plasma number. These are some of |
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| 08:38 | basic things. And now when we about ions crossing across plasma membrane, |
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| 08:47 | of these forces, the chemical gradients gradient, the chemical force and electrical |
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| 08:57 | charge and the battery forces now come play. So the Librium potential forgiven |
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| 09:04 | on E. Is a point at diffusion allow. And electrical forces are |
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| 09:11 | and opposite to each other and therefore is no net movement of ions across |
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| 09:17 | member. I also still moving across channels in the plasma membrane but there |
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| 09:24 | no net movement favoring more flowing in direction capacity or outside or inside. |
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| 09:36 | you have a movement let's say potassium in high concentration on the inside and |
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| 09:44 | you have an A minus some proteins are negatively charged and we're trapped on |
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| 09:50 | inside and they cannot, they they cannot cross let's say the potassium |
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| 09:57 | is open. potassium starts crossing down chemical concentration gradient but at some point |
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| 10:06 | is accumulation of positive charge by potassium on this side of the plasma membrane |
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| 10:17 | discharge not the concentration not the amount islands but the polarity. The charge |
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| 10:24 | the potassium builds up on this side the membrane starts repelling potassium against its |
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| 10:33 | concentration gradient. At this point the force repelling the charge protesting to go |
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| 10:42 | in. And the chemical number of saying we need to get diluted are |
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| 10:50 | to each other and forest. That's equilibrium potential. We will talk about |
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| 11:00 | I mentioned already how you have separation charge across plasma membrane and all of |
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| 11:08 | charges accumulated on this small narrow foster , bilateral. If you look inside |
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| 11:16 | cell and let's say you penetrate a the lectured and inside the south that |
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| 11:24 | plus and minuses actually neutral in the and the core of the south and |
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| 11:30 | charge on the outside and this acquis and the liquid is also neutral. |
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| 11:35 | the charge the membrane is actually The difference the plasma membrane overall what |
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| 11:44 | plasma membrane has is dictated by several species. Not just one potassium but |
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| 11:51 | difference in the plasma membrane voltage and equilibrium or reversal potential for an individual |
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| 12:02 | is what we call a driving And we'll talk about this in the |
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| 12:08 | . Mhm. The apply only concentrations known we can calculate equilibrium potentials for |
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| 12:17 | given ill. So we know these and by the way so this is |
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| 12:22 | demonstration that it's not potassium specific sodium is abundant sodium chloride. A salty |
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| 12:31 | basically on the outside of the sodium is going to be driven into |
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| 12:35 | south but positive charge accumulation from sodium start repealing it back. So electrical |
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| 12:45 | will start repelling sodium back and that believe in potential. So you have |
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| 12:53 | even distribution of charge and ionic palms bionic parts if you remember they use |
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| 13:03 | ATP and they work against concentration gradient that's all. They just need a |
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| 13:09 | and they'll just turn for every two I honestly bring inside they're gonna take |
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| 13:16 | your mouth two and three out to potassium three out. Then it's the |
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| 13:23 | diagram that we looked at last black and there's basically a couple of ways |
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| 13:31 | you can look at milan moller for eye on or a ratio of that |
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| 13:38 | on on the outside of the cell the inside of the south. So |
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| 13:42 | basically 20 times more potassium concentration on inside of the south versus the outside |
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| 13:50 | the cell. Or 100 million moller the inside versus five either way. |
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| 13:56 | that's just going to play into the for and equilibrium potential for each eye |
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| 14:03 | and you can see that each eye potassium sodium calcium and fluoride Has its |
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| 14:10 | value for the 2nd Librium potential. this is where we're getting at. |
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| 14:16 | do we calculate this value? Why this value important? What does this |
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| 14:22 | mean? And we'll come to Mhm a couple of times and right |
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| 14:31 | . So the nonstick equation is what you to calculate the equilibrium potential, |
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| 14:38 | potential or reversal potential as a call potential. Because the ion direction actually |
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| 14:46 | reverses in the opposite direction of the . Nurse equation is E for an |
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| 14:53 | ion is equal 2303. R. . Z. F log ion concentration |
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| 15:02 | the outside versus higher concentration on the . Where r. Is the gas |
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| 15:08 | T. Is the absolute temperature. course temperature in this case that we |
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| 15:15 | this physiological 37 C body temperature Is the valiant or the charge of |
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| 15:24 | ion and atmosphere. Day constant log and law algorithm of ion. And |
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| 15:32 | this case we can plug in one our four ionic species plug in potassium |
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| 15:38 | potassium on the outside versus potassium on inside. So you can look at |
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| 15:47 | of the details here. We're not for deriving this equation. You're responsible |
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| 15:52 | knowing the most important variables in this and that which for example was a |
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| 16:00 | temperature. You should know it not in Fahrenheit button centigrade to and This |
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| 16:08 | portion 2303 Now gets abbreviated and collapsed 61 50 for mm This is constant |
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| 16:31 | Valence. Okay, so there's two in this equation valence and then the |
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| 16:38 | and we set the temperature is So these we know all of these |
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| 16:41 | . If we take the mama Vaillant such as potassium and we plug in |
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| 16:51 | concentration On the outside vs inside. abbreviate we first of all, we |
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| 16:57 | this 2303 are TCF to log potassium the outside versus inside. And now |
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| 17:04 | of plugging in Individual Malamala Values, I told you there's a ratio of |
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| 17:12 | , 20 times more potassium on the of the cell versus the outside. |
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| 17:17 | so in this case you just plug . Yeah. Mhm one on the |
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| 17:27 | and 20 On the inside for potassium take a log of that 61-54 million |
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| 17:36 | becomes the value when you abbreviate this uh variables together. And you have |
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| 17:44 | concentration log Gives you -80 million volts potassium equilibrium potential. So this is |
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| 17:54 | you calculate it for potassium. If calculate it for sodium, you calculated |
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| 18:00 | the same way. If you calculate for chloride, this sign changes into |
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| 18:06 | because the valence chloride is negative For , this changes into 30.77 because calcium |
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| 18:19 | a Duyvil in castile. So it divided by two 61.54. And so |
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| 18:29 | this equation you're now able to calculate equilibrium potential for each individual ion And |
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| 18:42 | reversal equilibrium or norms potential is Almost 90. Again it varies sodium |
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| 18:50 | , 55 positive, 65, Calcium 123. 23. And remember calcium |
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| 18:57 | the highest disparity and concentration across plasma . And I also stressed in the |
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| 19:04 | that calcium is very tightly regulated inside cytoplasm because it acts as a secondary |
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| 19:11 | , can also regulate the secular fusion neurotransmitter release. So it gets bound |
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| 19:17 | by a lot of calcium patrolling calcium protein speculators and that is that is |
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| 19:26 | . But so this is how we uh nursed potential. Now we know |
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| 19:37 | to calculate equilibrium or reversal potential for ions. How do we calculate resting |
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| 19:44 | and potential Rusting member and potential is using the Gold one equation and the |
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| 19:52 | equation is essentially a variation of the depression. You have the same RTZ |
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| 20:02 | variables. You have the same 16 million volt abbreviation here log the two |
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| 20:12 | that are different about the golden Those two things are that golden equation |
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| 20:20 | more than one ion you have sodium and potassium ana Number one. |
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| 20:31 | 2, it has another variable. that's permeability. How permeable is the |
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| 20:41 | to that ion? Permeability is whether channel for that ion is open. |
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| 20:46 | the channels are all open, the is high. If the channels are |
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| 20:51 | , the permeability is low. So member and potentials. The cells are |
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| 20:59 | with potassium. It's closer to the potential for potassium but at the same |
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| 21:09 | it's most permeable to potassium and the is slowly leaking potassium addressed so it's |
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| 21:17 | permissible to potassium. So addressed, number of potential is dominated. My |
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| 21:24 | islands. But once the cell d polarizing sodium channels and more sodium |
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| 21:33 | and more sodium channels open and the becomes mostly permissible to sodium and sodium |
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| 21:41 | is dominating the deep polarization during the phase of the action potential. But |
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| 21:49 | you were to plug in at the premier ability for potassium is |
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| 21:54 | In fact it's 40 times greater than sodium addressing number and potential. And |
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| 22:00 | you plug in the values for potassium concentration values here and calculate this. |
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| 22:09 | get a number of potential. So most important ions that influenced the membrane |
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| 22:16 | . The sodium and potassium too small chloride. And you can plug in |
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| 22:22 | that chloride to these two ions in equation and see if it will change |
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| 22:27 | member in potential by a lot. it will not because it's low permeability |
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| 22:33 | chloride. So you can have different high concentration of an iron on the |
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| 22:42 | . But if you have low permeability channels are closed for that i on |
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| 22:51 | the value here is very low, small and the contribution and the change |
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| 22:57 | the membrane contribution to the member and is also loan if you change the |
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| 23:07 | Okay you change the permeability to sodium of 1-40. Now sodium is very |
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| 23:14 | in charge of changing the overall numbering which is VM. Okay. So |
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| 23:21 | . K. Or E N. R neurons potentials equilibrium potentials. And |
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| 23:29 | . Is member and potential which incorporates ionic species in determining its potential |
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| 23:38 | Mhm. Is it a major difference that we're talking about here now the |
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| 23:50 | concentration from the outside of the cell tightly regulated and if you recall we |
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| 23:57 | about astra sites and we said that have these processes and one of the |
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| 24:04 | of these processes is to regulate synaptic . So now the genesis and ethic |
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| 24:13 | . The other part of these processes involved in the blood brain barrier. |
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| 24:21 | . Overall astrocytes have this extensive processes interact and are interconnected with other exercise |
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| 24:32 | the brain through electrical junctions that we the gap junctions. So we'll discuss |
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| 24:38 | when we go later in the course not the transmission. So astra |
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| 24:46 | one of the things that they do they don't only regulate neurotransmitter. So |
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| 24:51 | look at their regulation of glutamate in as well as gather both excited to |
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| 24:57 | and their transmitters. But astra sites also regulate the local increases in ionic |
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| 25:07 | . If there is a lot of activity nearby, there's gonna be a |
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| 25:12 | of potassium from these neurons going onto outside of the south and the synapses |
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| 25:17 | this increase in extra cellular outside What it does is that regular potassium |
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| 25:25 | is about 3.5 to 5 million more here, which will keep the member |
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| 25:31 | potential value at -70 close to resting of potential. Yes. What happens |
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| 25:38 | the extra cellular outside potassium concentration increases 10, The 20 million moloch You |
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| 25:48 | this value here of about -45 -40 balls, which is the deep polarization |
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| 25:54 | is strong enough to start evoking an potential. So if you do not |
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| 26:01 | external ionic concentrations and this is an for potassium if you have rises and |
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| 26:10 | and you don't regulate extra cellular potassium , neurons keep the polarizing firing synchronizing |
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| 26:19 | causing abnormal activity. In fact this one of the pathological models for evoking |
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| 26:25 | like activity or abnormal hyperactivity and hyper of neurons in the brain astra sides |
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| 26:33 | project there and feet and slur This increased concentrations of potassium distributed widely |
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| 26:42 | their processes and distributed widely through the . That ostro citic networks, avoiding |
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| 26:53 | concentration increases in this case for potassium , kind of siphoning and specially buffering |
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| 27:02 | concentration instead of allowing for that potassium stay within a given brain region, |
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| 27:09 | would mean that those neurons are getting and more active, more and more |
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| 27:13 | , more and more active, more more synchronized that activity can spread astra |
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| 27:19 | play this role of regulating and by and buffering spatially basically distributing specially this |
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| 27:28 | concentrations of potassium mile they regulate and in part the homeless stasis or the |
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| 27:37 | of the ions around the synopsis of brain. Uh huh. Uh |
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| 27:53 | All right. So I'm gonna pause little bit here. Yeah, if |
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| 28:02 | go to the lecture notes. You will find a file in your |
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| 28:17 | says action potential and equilibrium potentials. huh. Then what what I do |
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| 28:25 | is actually a draw it out, you know when you're doing online you |
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| 28:29 | dry it online. Uh but it's drawn. So what I would like |
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| 28:40 | you to do is to draw this , you know you take great |
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| 28:45 | If you draw things, if you arrows to put a different colour, |
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| 28:50 | something then you're taking good notes. all of these things is what stimulating |
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| 28:56 | sensory uh information inputs and allow you memorize things better. So what I |
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| 29:05 | here is I've created a millennial scale . This is the number of |
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| 29:12 | Our MP stands for arresting members and . And so the resting membrane potential |
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| 29:18 | about -65. Mobile right? This the equilibrium potential for calcium about 120 |
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| 29:28 | volts. This is a equilibrium potential sodium but positive 55 million balls, |
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| 29:37 | potential for chloride from -70 or The equilibrium potential for potassium. |
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| 29:46 | the book and the calculation that showed previous slides at -80. Um now |
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| 29:51 | U -19. This is not a question of the exams at the stadium |
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| 29:57 | . I got you know, the is that take home messages from the |
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| 30:04 | questions are going to be framed in way that you're going to be able |
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| 30:08 | clearly know and decide for the difference what I'm asking you. If you |
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| 30:12 | tell the difference between reversal potential and and potassium, you have a |
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| 30:17 | But it isn't going to be a if it's 65 or 75 reversal for |
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| 30:22 | for something resting membrane potential for So, uh now this is your |
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| 30:30 | potentials. All right, these are potential sort of derived from learns the |
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| 30:37 | . This is the member in potential is VR Viana is derived from Goldman |
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| 30:45 | equation of So, addressing member in . This neuron it's not ever a |
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| 30:54 | line neuron membrane potential. And this number of potential fluctuates 65,067, and |
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| 31:05 | neurons start receiving inputs, start receiving positive inputs, illuminates an absence which |
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| 31:13 | deep polarization, us reminder 16 17 minus 65 then it receives inhibitor and |
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| 31:22 | and it causes hyper polarization. So goes down again like a stock market |
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| 31:29 | that and then boom. And that's you have to cash out or hope |
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| 31:35 | keeps going. But with action potential you get enough of the deep polarization |
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| 31:41 | would be glutamate excitation. And you not the resting membrane potential but the |
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| 31:49 | potential threshold Which is the value of -45 normals you have this boom, |
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| 31:58 | produce an action production and you have rising phase of the action potential where |
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| 32:04 | have a lot of influx of sodium you have the following phase of the |
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| 32:09 | potential where you have a lot of reflux. So if addressing membrane |
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| 32:18 | resting membrane potential is dominated by potassium because the membrane is leaky and potassium |
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| 32:25 | that are open and its most permeable potassium at rest at R. And |
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| 32:34 | . Once it reaches the action potential , the cell membrane channels for sodium |
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| 32:41 | all open And that cell is most to sodium allowing for sodium to Russia |
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| 32:48 | causes very fast deep polarization which almost the equilibrium potential sodium but it reverses |
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| 33:00 | and drives down and you have the phase where you have a potassium influx |
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| 33:07 | the cell membrane. Now sodium channels closing potassium channels are all opening |
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| 33:14 | potassium is flexing and is driving the and potential to the equilibrium potential value |
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| 33:21 | potassium. So if you open all sodium channels, what sodium wants to |
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| 33:26 | is what's the reasons equilibrium potential It to drive the membrane into positive |
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| 33:35 | They then close these channels and we'll about these dynamics maybe later today, |
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| 33:41 | on Wednesday. Now potassium channels are . If you open all potassium |
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| 33:48 | all potassium wants to do is drive member and potential down to its equilibrium |
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| 33:53 | allowance. Yes. Yeah. So come back and talk about the channel |
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| 34:04 | . But this person that I highlight a person that like to finish talking |
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| 34:12 | the resting membrane potential And the whole behind trying to determine what precisely is |
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| 34:20 | structure of these channels and dr roderick which is shown here is the person |
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| 34:32 | worked with channels. And he is a sort of an inspirational person from |
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| 34:38 | career perspective, he was a medical and he was not really satisfied and |
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| 34:46 | decided to become a a geneticist, electro physiologist really and studies potassium channel |
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| 34:56 | and that wasn't enough. So he to pick up X ray crystallography which |
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| 35:05 | a whole different beast being an MD medical doctor in Harvard too. Having |
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| 35:12 | research lab during electrophysiology and flies And channels using toxins and genetics to preparing |
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| 35:22 | for a massive biochemistry preparations. So very very precise and detailed that it's |
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| 35:27 | art and science on the zone. like doing another degree. It's like |
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| 35:31 | you finished Andy you did one more and then you decided I'm going to |
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| 35:35 | another ph d. Yeah you know that's the drive that this guy had |
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| 35:41 | Mackinnon you use genetic mutations use using . Toxins will bind to certain parts |
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| 35:50 | the channels And there are a lot toxins in nature from spiders and from |
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| 35:57 | different creatures in the world there are specific to certain ionic channels that will |
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| 36:04 | to certain ionic channels. So shaken were shaker flies, they were shaking |
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| 36:10 | they had a mutation of potassium channel in fact it became sort of a |
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| 36:15 | for hyperactivity and even seizure like We have a lot of conservative amino |
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| 36:24 | across species have a lot of conservative . So when you're working with fruit |
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| 36:33 | it's not only the electro physiological behaviors you will see the similar in the |
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| 36:38 | a capital brain slice and then the human brain, but it's also the |
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| 36:44 | of the code that are preserved which important. That means that if a |
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| 36:51 | , if something binds in three dimensions a channel and you know the sequence |
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| 36:59 | which it binds and that sequence is in humans. You know that that |
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| 37:04 | also has an ability to buy into same sequence preserved sequence in humans or |
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| 37:13 | higher or other lower order seasons. he saw that this channel has sub |
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| 37:23 | that there is this hairpin loop. hairpin loop is responsible for the filtration |
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| 37:30 | the seething capability and selectivity of the channel. Poor and toxins and electrophysiology |
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| 37:41 | necessary for him to derive. Why you use toxins? Why would you |
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| 37:46 | electrophysiology? Because if you don't fly toxin, you know, sequence there's |
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| 37:52 | things you can do you can do directed me to genesis, which means |
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| 37:56 | can mutate a science on this long acid protein structure. You mutate a |
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| 38:06 | , you can see how it affects channel. Is this channel conducting more |
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| 38:11 | ions of potassium channels islands. you know how it affects the |
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| 38:17 | Then you say, I'm going to a toxin and binds that want to |
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| 38:20 | where they binds a certain sequence where blocks the channel certain toxins where it |
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| 38:28 | ? You're starting to get to what slowly starting to get through the structure |
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| 38:33 | that channel. What are the important which sequences the gatekeeper. It's not |
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| 38:40 | entire protein that gets bound by an by a toxin by molecule. It |
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| 38:47 | be a small sequence that gets bound that's the important one that closes or |
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| 38:54 | . That channel channel has other functions involved in in cellular processes. But |
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| 39:01 | or closing could be down to that key hole in the big door and |
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| 39:08 | you don't have the right key, even the key but the right key |
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| 39:14 | , not even the actual handle or the keyhole if you don't have it's |
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| 39:19 | that the door won't open. But you do and you figure it out |
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| 39:24 | you're on to something. Now you say that this sequence this toxin that |
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| 39:30 | the sequence is responsible for opening and . This one is responsible for partially |
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| 39:38 | this sequence is responsible for partially If I do this to this three |
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| 39:44 | structure it keeps the channel open So you're now calculating out but it's |
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| 39:52 | enough to visualize the structure and that's he is driven by. And that's |
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| 39:59 | he picks up factory crystallography and says actually going to I want to see |
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| 40:04 | . I want to see the produce next week crystallography is you project X |
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| 40:09 | through a protein that's trapped in the . And it's like I said, |
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| 40:14 | takes a PhD to even trap small on the crystal and then you project |
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| 40:20 | X rays. You calculate out based calculations based on national visualization. Now |
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| 40:28 | have this wonderful structure of the potassium , general atomic structure of potassium. |
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| 40:38 | it takes a lot, it takes lot of passion. And the one |
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| 40:45 | the most important take home messages for is you pursue your passion and sometimes |
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| 40:54 | Ramona alcohol, you have to disagree your boss who's Camelia Goldie, but |
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| 41:01 | are way more famous and and you right actually that to pursue a |
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| 41:11 | it's not the degree degree is a to get to what you really want |
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| 41:17 | do and there's twists in the career when you think I'm striving to do |
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| 41:29 | , it's not the end And a of people don't retire at 70 and |
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| 41:36 | of them pick up a new degree 65, so it's a winding road |
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| 41:43 | it's the, it's the passion and goal to which you're trying to get |
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| 41:48 | ultimately. And if you look at of the even entrepreneurial success stories, |
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| 41:57 | hear about people when they make a dollars and they're happy and famous, |
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| 42:02 | maybe they're getting divorced, but you , they come across as famous and |
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| 42:10 | If you don't hear about 15 businesses they fail that miserably before the strike |
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| 42:18 | this one, they persisted. So same way goes with degrees and sometimes |
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| 42:24 | not even the degrees, it's the goal. And there are many different |
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| 42:29 | in this winding road to get the . The door action potential. The |
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| 42:37 | phase, the overshoot. When it above zero mobiles. The falling phase |
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| 42:43 | undershoot when it goes below resting membrane is more hyper polarized and resting membrane |
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| 42:49 | . The most exciting things that happens the membrane is the action protection. |
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| 42:54 | of the action is in the is the you're on. Is that that |
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| 43:00 | ? So for this when you follow recording for a second. Mhm mm |
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| 43:15 | . The capital partners body fans and didn't and I always be aliens from |
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| 43:21 | world. Mhm. So perhaps it's surprising that for a long time for |
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| 43:27 | to discover that there are fundamental similarities the other systems of care for bars |
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| 43:32 | restaurants. Yeah. Yes. It's condition of the useful difference in our |
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| 43:41 | which enables scientists to undertake research has to a growing understanding of the mechanisms |
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| 43:47 | our own system to control the contraction the natural numbers. Using precautions as |
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| 43:59 | archive film shows a simultaneously tracking his muscles even a moderately sites with injected |
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| 44:06 | huge amount of water with great Yeah. Oh In the mid 1930s |
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| 44:16 | Professor Jason Johnson was engaged in the of squeezing me. Mhm. Young |
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| 44:23 | an array of large tubular structures, as much of the Middle East in |
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| 44:28 | squeeze metal and these structures will never with line. It would not be |
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| 44:35 | from their similarities surrounding the advisers. , but there must be single |
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| 44:40 | Giant Exxon transmitted doctors from the concentration nervous tissue called Listeria Gambia to the |
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| 44:47 | muscles using electrodes. He stimulated the the proprietors and found that he had |
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| 44:58 | produced large muscle contraction in the battle the large tubular structures remain in his |
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| 45:09 | . Yeah, So these were indeed accidents. Scientists quickly appreciated the significance |
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| 45:19 | young finding. But here at last an excellent large and robust enough to |
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| 45:24 | what the needs are available at the and one of the Divine for several |
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| 45:28 | when isolated from the others. The into the contents of the journal Exxon |
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| 45:38 | be removed and analyzed into the discovery sodium more concentrated outside of themselves and |
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| 45:45 | mines more concentrated inside by reading the acts on solutions and precisely the chemical |
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| 45:55 | experimenters were able to unravel the mechanisms iron transport across the the german tax |
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| 46:06 | large enough and robust enough finding electrodes be inserted through the cell membrane and |
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| 46:12 | the accident. Right in these early . The fine glass tube was first |
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| 46:24 | act on and to hero fret. like a fishing. Not then the |
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| 46:48 | was used to introduce a fine won electorate which goes into the inside and |
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| 46:53 | outside could be measured. But the of the early implants was fun too |
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| 47:00 | for detailed study with any of the measuring devices of the 1930s, It |
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| 47:07 | until the 1950s following the wartime improvement electronic equipment such as the cattle |
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| 47:12 | To escape that major progress was Scientists found a million transmitted aka, |
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| 47:22 | way in electrical potential that this fall action potential generated maybe by transient movements |
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| 47:30 | Syrian a taxi, um, islands the middle membrane. Research in square |
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| 47:37 | german Exxon and gravel makers and quotation of the action potential. This understanding |
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| 47:45 | directly to the development of drugs that action potential formation. So actors, |
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| 47:51 | and state now used routinely painters in and minor surgery. White. |
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| 47:58 | so, Okay, that's |
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