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00:00 | action. So we're back on this . This is an inspirational story, |
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00:06 | . Everyone to learn how Thio basically Stop it Something but pursue something not |
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00:15 | it. Getting a degree, not it. Making some project. But |
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00:22 | getting driven. Thio solve more complicated to get Thio more details about what |
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00:32 | in nature and things like that. Roderick MacKinnon All right, before we |
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00:37 | into into the action potential lecture wanna out that I have a couple of |
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00:44 | , walk you through and let me this should switch now because what I |
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00:50 | to finish, actually talking about resting and potential is that what we're building |
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00:56 | an understanding that membrane is like a . The plasma membrane is like a |
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01:07 | that you have an extra cellular aside you have these channels and these channels |
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01:15 | like conductors. So here, for , you have on top potassium channels |
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01:21 | they are for G K, which for potassium conductors, or it's a |
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01:29 | . So this symbol here is a symbol. Yeah, this symbol |
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01:39 | I'll draw for you and everyone should this. This is the physics language |
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01:46 | the membrane circuit. Yeah, this the symbol for resistor. It's on |
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02:04 | slide to okay, then you have symbol for battery. Okay, this |
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02:25 | a symbol for battery. Okay, , G there is because G is |
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02:41 | inverse of the resistance. So each the ions essentially has arisen is serves |
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02:47 | a resistor channel. If it's the resistance is slow and ions cross |
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02:55 | the channel. If the resistance is , the channels air closed and then |
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03:01 | have a battery and the battery is electrochemical driving force again. Electrochemical driving |
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03:09 | for each ion can be represented by M minus equilibrium potential forgiven ion So |
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03:18 | potential minus equilibrium. Potential forgiven. driving force equals I. R. |
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03:24 | just basically rewrite arms law. But we incorporated equilibrium potential for potassium. |
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03:34 | conduct intense. Okay can be calculated each one of the ions. And |
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03:42 | we look on the plasma membrane, it's not just potassium channels that you |
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03:47 | on top, but you have potassium and chloride channels, and each |
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03:54 | of these have their own conductor and actually a resistor conductor and it za |
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04:03 | conductor, meaning that Sometimes the channel open and the conduct Ince's high and |
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04:08 | the channel is closed in the Ince's low and each one of them |
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04:13 | their own respective batteries, with the and the negative end shown here accordingly |
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04:19 | sodium, potassium and chloride ions. huh. So to calculate the overall |
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04:27 | ins forgiven High on, for for potassium ion depends on the number |
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04:35 | potassium channels and conductors. Foran, potassium channel all right, and the |
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04:45 | Grady int and potential difference is illustrated top here because we have a current |
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04:53 | potassium, I is equal the are in this case, I is |
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05:04 | D. M. The current for is equal conductors for potassium times, |
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05:13 | membrane potential minus the conductors for potassium , the equilibrium potential or, in |
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05:21 | words, conducting for potassium times its force. So the total current from |
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05:29 | is conducting for individual potassium channel Its driving force and the driving force |
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05:36 | the difference between the membrane potential and equilibrium potential for potassium and below the |
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05:44 | . Ince's the total off the individual channels times the total number of channels |
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05:50 | are present true. So now another important subject to discuss when we discuss |
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05:59 | membrane, this capacitance. It's the that plasma membranes are very good |
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06:06 | There's certain qualities to be a good . To be a good capacitor, |
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06:12 | need to have a lot of surface where you can store charge to be |
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06:19 | good capacitor. You should have the plates of the capacitor very close to |
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06:27 | other. And such is the case plasma membrane. Yeah, yeah, |
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06:41 | is the symbol for resistor. This a symbol for the battery, and |
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06:49 | was a symbol for capacitor in the , which shows a storage of positive |
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06:55 | and the storage of negative charge. what? That's exactly what happens for |
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07:00 | membrane. It stores a lot of negative charge on the on the outside |
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07:07 | the inside of the membrane and a of the positive charge on the outside |
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07:12 | the membrane. So it's very good . Also, the capacitor plates is |
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07:18 | fossil lipid bi layer, so the plates are very close to each other |
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07:23 | then discharge. There's a lot of because there's a lot of surface |
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07:27 | There's a lot of them drives them experience creating surface area for store storage |
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07:33 | the charge. But the discharge is quick across the to place because the |
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07:39 | is very short. Uh huh. these are all of the features of |
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07:44 | good capacitor. Plasma membrane is a good capacitor. This is on the |
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07:50 | . What you have is an injection the awkward corner inward. Current in |
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07:56 | one would have shown is that if just placed on electrode in a solution |
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08:01 | there was no resistance, there was plasma membrane across. Then you would |
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08:06 | the square wise like response. You , these squares that are stacked on |
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08:10 | of each other showed current outward or n word and the measure of the |
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08:16 | and nano ampere 0.5 nanogram pairs. if you inject that current into the |
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08:23 | just like we were looking at that off the car and through the electrodes |
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08:28 | the neurons, you will not get square box like response. You will |
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08:34 | a response as in a two, you can see that there is a |
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08:38 | up of charge of the plasma This is the charging up of the |
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08:45 | . Okay. And then is you the stimulation, which is this this |
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08:52 | end here on these curves. Then is a slow decline, and that |
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08:58 | because the discharge takes some time But that time we're talking here is |
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09:05 | . And that's why the plasma number a good capacitor is it takes a |
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09:09 | milliseconds to fully charge them up. this rise in this, uh, |
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09:15 | shape of the curve which is really off voltage across plasma membrane. As |
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09:21 | inject the square wave current from your equipment into the cell, the cell's |
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09:29 | and capacity to properties shape it into response that you've seen 82 It takes |
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09:35 | to charge up negative charge. And when you release it, it takes |
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09:39 | for it to come back to resting and potential of minus 60 on the |
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09:45 | . What you have is you have ivy curve. This on the right |
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09:51 | B is called an ivy curve. this is is there is voltage on |
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09:59 | X axis in Milan balls and on Y axis. You have current in |
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10:06 | AM Paris, and this is called linear or Ahm IQ ivy curve |
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10:14 | I stands for current, the for . So Ivy Curve. This is |
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10:21 | linear curve, which means that for same amount of current that gets passed |
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10:26 | the cell, let's say 15 positive on Pierce changes the cell from minus |
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10:35 | to minus 55. Positive one and Paris Changes is 2 50 positive to |
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10:42 | it thio minus 40 over here. , so if you inject negative current |
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10:53 | one Nana am Perry's she had changed minus 60 to minus 70 minus point |
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10:59 | him from minus 70 to minus So this is a linear or comic |
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11:04 | curve of the off off a particular . But in reality, all of |
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11:10 | channels have different shapes. Curves that call rectifying curves that will discuss, |
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11:19 | , let's see that we'll discuss in next lecture, Actually, but now |
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11:24 | talk about the capacitance a little All right, you have the are |
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11:29 | here, which stands for the internal or resistance in terms inside of the |
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11:36 | . The RN depends on the resting density. How many channels how densely |
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11:43 | is that membrane with channels, it on the membrane surface area. That |
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11:49 | the small neurons will have very high and low conduct INTs. Large neurons |
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11:57 | have low resistance or lower resistance. when you're calculating the the resistance off |
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12:09 | inside of the South, you have take into consideration the resistance of the |
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12:15 | . Okay, this is where resistance of the membrane over four pi a |
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12:23 | where a stands for radius of hysterical . Yeah, so the larger the |
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12:35 | , the larger the a, the that are in. Yeah, the |
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12:43 | the sell, the smaller the inside of the cell for capacitance capacitance on |
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12:53 | opposite side. It's very different for . Actually, with you have described |
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13:02 | the right is First of all, change in voltage can also be |
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13:07 | Measured in the change in Q Q for charge. Another term Q stands |
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13:16 | charge oversee, which is our which stands for capacitor. In other |
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13:24 | , to change the Walters, you Thio Cross to have to have the |
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13:29 | to be added or removed from one the other plate of the capacity |
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13:36 | And so if we look at the of the capacitor now, it's very |
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13:41 | because the the input the capacitance input the South depends on the capacitance of |
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13:48 | membrane times, the radius of the neural. That means the larger the |
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13:57 | of the spherical neuron. The larger the capacitance. Mhm. That's the |
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14:05 | from the resistance. Mhm resistance. larger the A, the smaller the |
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14:14 | capacitance, the larger the A, larger the capacitance mawr surface area. |
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14:20 | store the charge, you can draw a number and equivalent circuit here, |
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14:27 | is also here. This is what mean by membrane equivalent circuits. This |
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14:33 | a membrane equivalent circuit where you represent membrane as if it was an electrical |
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14:41 | physics circuit. So you put your cellular side but one side of the |
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14:51 | . Extra salary on the other On the side of Plas mix |
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14:54 | you have resistors. A year for eye on battery is here for each |
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15:00 | on, and there's nothing here. really passive flocks here. If you |
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15:06 | at the circuit, there's not much going on. Now let's look at |
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15:10 | circuit below. This shows passive and Fluxus. What I mean by that |
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15:18 | that there's actual flux here. First all, there's an added component here |
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15:23 | the plasma membrane that makes this representation realistic. And this added component is |
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15:30 | M, which stands for numbering capacitance on the side of Plas mix side |
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15:37 | of negative charge and on the extra aside, accumulation of the positive charge |
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15:44 | is here You have a plump here pump using energy. What is the |
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15:50 | doing? Look at what the pump doing. Current i n a. |
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15:55 | . Slowing to the outside of the , there's lots of sodium on the |
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15:59 | , but remember, the pump is against concentration radiant, pushing sodium |
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16:06 | pushing potassium inside the south. Then have again the conduct INTs and the |
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16:13 | for each G. K for potassium folklore, a G n A for |
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16:21 | , and you have the direction of current flow here, too, so |
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16:23 | can see potassium ions so moving from , because there's a lot of potassium |
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16:28 | the inside to the outside, while sodium ions also positive charge of moving |
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16:34 | outside, where there's a lot of chloride to the inside of the |
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16:41 | So So this is membrane equivalent and this is the last one that |
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16:50 | wanna make about resting member and because before we talk about the |
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16:55 | potential is this is the permeability ratio potassium over sodium over chloride. The |
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17:06 | line shows the permeability ratio uh, , very high sodium, very low |
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17:15 | , very low. This is resting of potential that's driven by potassium is |
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17:22 | by potassium conducting. Remember, it's times higher addressing member and potential for |
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17:28 | . The second line shows a very ratio of permeability. Now you have |
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17:35 | times MAWR ratio 20 times mawr, for sodium versus potassium and the permeability |
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17:43 | chloride doesn't change. This illustrates action . This illustrates that during the action |
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17:52 | , the permeability ratio for potassium during rising face of the action potential remains |
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17:58 | one, while the permeability for sodium increases. And it doesn't really change |
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18:05 | chloride that month. So the last here again is a Goldman equation, |
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18:12 | it's also Goldman, Hodgkin and Cats . You can pull again chloride concentration |
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18:19 | you want to also see if chloride change much of the number of potential |
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18:25 | you have the values for permeability, for chloride here. Uh huh. |
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18:32 | the point is, that permeability ratio very much change for individual ions, |
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18:39 | on the state of a neuron. during the action potential, the permeability |
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18:43 | sodium is gonna skyrocket. And that going to very much change the membrane |
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18:49 | . Because imagine having a VM where for sodium is 0.4 here for P |
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18:58 | the VM on permeability for sodium actually 0.4 becomes 20 in this p value |
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19:06 | . All right, good deal. now we're done with the resting member |
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19:11 | potential. Let's try to understand how whole action for temps troll happens. |
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19:19 | by the way, I know that some of you, it's not very |
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19:22 | material. But for some of you are more biology frog, muscle minded |
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19:31 | and neuron firing minded, uh, , you know, chemistry people. |
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19:37 | might be a little bit more so we'll review some of these concepts |
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19:43 | . The basic things that we know action potential. Now we know a |
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19:47 | . We're coming from resting membrane During the rising phase of the |
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19:51 | potential crosses zero mila vault line when crosses the zero move offline. The |
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19:57 | of the action potential is referred to overshoot. And once it reaches about |
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20:04 | positive middle of all value, it returns started returning back through this falling |
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20:10 | of action potential. And it goes low resting member of potential, the |
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20:16 | resting member of potential. Because potassium now driving the science down Thio negative |
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20:22 | , overall number and potential, and experience an undershoot which goes below resting |
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20:28 | of potential and takes some number of to recover. So this process again |
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20:33 | just a matter off one too few in neuron in the heart action potential |
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20:42 | are quite different action potential so much . And primary focus here in this |
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20:48 | is actually neuron election potential. So confuse if you knew something about cardiac |
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20:54 | from previous courses. All right, gonna stop sharing for a second, |
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21:01 | , uh, I'm gonna see if can switch Thio a different. |
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21:16 | see, this is in your supplemental course, electro materials. That's |
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21:30 | uh, fascinating video off how this started happening. Our understanding off the |
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21:39 | dynamics off the action potential. it's pushed them. Of course, |
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21:50 | from another world. So perhaps it's surprising that it took a long time |
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21:55 | scientists to discover that there are fundamental between the nervous systems of careful parts |
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22:01 | vertebrates. Yet it was the recognition a useful difference in their nervous |
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22:10 | which enabled scientists to undertake research that led to a growing understanding of the |
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22:16 | controlling our own nervous system. The concerned the nerves that control the contraction |
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22:22 | the mental muscles used in jet As this archive film shows by simultaneously |
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22:31 | it's mental muscles. Even a moderately squid can inject a huge amount of |
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22:36 | with great force clear. In the 19 thirties, British zoologist professor |
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22:46 | Z Young was engaged in a study the squid's anatomy. Young observed an |
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22:53 | of large tubular structures, each as as a millimeter in diameter in the |
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22:58 | metal. As these structures were never with blood, they could not have |
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23:02 | blood vessels. From their similarity to nerve fighters, Young thought they must |
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23:08 | single neurons, giant axons. They're nerve impulses from a concentration of nervous |
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23:14 | called Estella ganglion to the mantle Using electrodes, he stimulated the surrounding |
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23:26 | fighters and found that he could only large muscle contractions in the metal when |
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23:31 | large tubular structures remained intact. So were indeed giant accents. Scientists quickly |
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23:47 | the significance of Young's finding. For . At last was an ax on |
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23:51 | and robust enough to investigate. With techniques available at the time and one |
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23:56 | survived for several hours when isolated from nucleus, the interest cellular contents of |
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24:06 | giant axon could be removed and leading to the discovery that sodium irons |
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24:11 | more concentrated outside the nerve cell and ions more concentrated inside by refilling the |
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24:21 | axons with solutions have precisely known chemical . Experimenters were able to unravel the |
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24:27 | of iron transport across membranes, the axons, the large enough and robust |
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24:38 | for fine electrodes to be inserted through cell membrane and into the Axa |
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24:49 | In these early techniques, a fine tube was first inserted into the ax |
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24:54 | and secured with threatened, then the was used to introduce a fine wire |
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25:20 | from which the voltage between the inside the outside could be measured. But |
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25:26 | formation of the nerve impulse was far rapid for detailed study with any of |
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25:31 | electrical measuring devices of the late 19 . It wasn't until the 19 |
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25:37 | following the wartime improvement of electronic equipment as the capital Greatest telescope, that |
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25:43 | progress was made. Scientists found that nerve impulse was transmitted as a characteristic |
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25:52 | of electrical potential that this all or action potential was generated mainly by transient |
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25:59 | of sodium and potassium ions across the membrane. Research on the squid's giant |
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26:07 | on unravel the mechanisms of the formation propagation of the nerve action potential. |
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26:13 | understanding led directly to the development of that block action, potential formation and |
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26:20 | actors local anesthetics now used routinely as in dentistry and minor surgery. |
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26:35 | that movie that we just watched on John Faxon physiology and is very revealing |
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26:43 | , essentially saying that not until 19 you even had the Silla scopes and |
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26:50 | to capture these action potentials. So development of the technology the electron ICS |
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26:57 | World War Two have actually contributed to advancement of the electric physiological science. |
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27:04 | in fact, it's interesting that some the electrophysiology circuits and connections air similar |
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27:11 | some of the submarine wiring that you in the military is still in |
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27:18 | This is voltage plan, but so gonna have to understand a little bit |
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27:22 | how old this clamp works in order understand how you measure this potential across |
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27:28 | membrane. But let's discuss a couple things 1st. 1st of all, |
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27:35 | the rising phase of the action potential already discussed. You have very high |
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27:41 | to sodium, so you have the influx, so sodium is going in |
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27:47 | influx during the rising phase of action . Do you remember what the equilibrium |
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27:54 | for sodium Waas? Wow, if don't, we can always go back |
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27:59 | few slides and remember it, but za positive value right in the |
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28:09 | so positive value equilibrium potential for sodium positive. 62 mil evolves, |
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28:17 | So what is happening here? What happening here is that during this rising |
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28:23 | , there is a high permeability for and very high driving force. The |
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28:29 | potential for sodium is positive. 55 60. That means sodium is gonna |
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28:36 | driven inside until it tries to reach equilibrium potential. But it doesn't quite |
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28:42 | equilibrium potential in the top of the potentials approximately plus 35 plus 30 million |
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28:50 | , and it starts reversing back. starts going into the falling phase. |
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28:56 | that's because as the membrane potential becomes and more positive, there is less |
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29:03 | less dry for sodium to go inside less less sodium channels from the ability |
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29:11 | off the decrease drive. Because sodium during the rising phase of the action |
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29:17 | is actually a positive feedback mechanism, sodium or deep polarization, more deep |
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29:24 | . More sodium channels open more sodium open more sodium or deep polarization. |
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29:29 | deep polarization. More sodium channels open sodium, so it should be going |
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29:35 | the way until it reaches equilibrium. for sodium here, the peak of |
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29:39 | action potential in the membrane potential. it does not because driving force reduces |
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29:45 | sodium and at the same time as member and becomes mawr positive, more |
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29:50 | , polarized the driving force for potassium minus 80 minus 90. That means |
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29:57 | all of a sudden the roles and driving force a switch, and the |
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30:01 | force for potassium becomes greater trying to potassium now. Okay, Driving potassium |
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30:09 | the potassium concentration sodium is going Potassium is going out. There is |
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30:16 | flux of potassium or e flux in of sodium during rising phase and e |
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30:23 | , or leaving of the potassium during falling face. To reshuffle the positive |
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30:29 | negative charge across plasma membrane and It becomes the most permissible ion during |
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30:35 | falling phase of the action potential, it is so powerful that it tries |
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30:41 | draw. It is a Librium potential minus 80 minus 90 and remember that |
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30:47 | the membrane is most memorable for so it almost succeeds to drive it |
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30:52 | the Librium potential. During this undershoot , and then with the help of |
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30:57 | N a k a purpose pump, have the slow recovery of the plasma |
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31:03 | into the previous resting membrane potential value about minus 65 million balls. So |
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31:09 | the next lecture, what we'll do I'll actually show you how I draw |
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31:14 | of these, uh, action potentials some of the the illustrations that I |
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31:21 | on my own notes that helped me keep track and understand all of the |
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31:26 | potential dynamics. So at this I'm going thio shock if there is |
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31:36 | questions, So where do we find fines? They are all on the |
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31:46 | . 50 fuel amounts? Yes. again, the question is about the |
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31:52 | potential value, and that might be variation between slides. And that's because |
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31:57 | very between South. So it's very . Calculations is very between textbooks, |
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32:03 | it's all within the ballpark. Is caused by 62 Millers? It caused |
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32:08 | later increased probability to potassium. so I'm not sure. I guess |
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32:18 | question was a little bit while so I'm not sure within what |
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32:21 | if you want to repeat it. I think one of the important take |
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32:26 | message is this. Permeability for potassium very high, addressed on that permeability |
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32:32 | very high for sodium during the rising of action potential, and then |
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32:36 | it becomes very high for potassium during falling phase of the action potential. |
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32:42 | if you just keep similar concentrations of and sodium on the inside versus the |
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32:49 | and you change the permeability for these , you will see how the number |
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32:53 | potential changes accord anyway. Okay, determines how soon one action potential can |
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33:03 | a lotta in regards to the falling ? Uh, not exactly. |
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33:09 | there is a absolute and relative refractory . So during the falling phase of |
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33:18 | action potential, you cannot generate another potential. Another important feature that was |
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33:24 | in the video is this action potential all or non event. Once you |
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33:28 | generating it, it goes all the to the spike. It has to |
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33:31 | back in order to generate the next potential. But that period, the |
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33:37 | refractory period when it cannot generate action , is followed by a relative refractory |
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33:43 | . That's when the plasma membrane is re balanced from this undershoot back into |
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33:48 | resting member and potential value. And that period of the stimulus is strong |
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33:53 | this refractory period, relatively factory you can generate another action potential. |
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34:00 | , lot of it depends how fast can generate or How short is this |
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34:05 | period depends very much on the channel and individual cells. And as you |
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34:12 | , we talked about inhibitory Interneuron from fact that they can actually produce up |
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34:17 | 600 actual potentials. A second criminal Torrey Sauce really cannot go that |
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34:24 | You can drive them at maybe 40 60 spikes per second or action potentials |
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34:30 | second. That is because they have much longer refractory period to, and |
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34:35 | depends on the channel composition and So how do we prepare, for |
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34:43 | , reading power ports to your commanders read a book? A Swell. |
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34:47 | suggest that I think at the beginning the course, also Thio. Best |
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34:52 | to do this is Thio. Attend lectures, check your lecture notes, |
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35:00 | notes and also, um, view Electra videos that are on video |
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35:11 | Okay, so if you do that attend the review and review the material |
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35:21 | the exam, so the best is you review everything. If you look |
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35:27 | the but the the still of If you review, let's see if |
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35:37 | review everything on the syllabus for all the eight lectures September 20 By September |
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35:50 | will have midterm exam review session. if you look at the materials you're |
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35:58 | the let's just review the videos, have any questions? Bring your questions |
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36:03 | their exam review session, and then should be in a really good |
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36:09 | so Okay, great. This, ah. Wednesday, I will continue |
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36:21 | about that action potential on. pretty much. Trying to catch up |
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36:26 | the rest of the material over the couple of lecture says is listed on |
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36:31 | syllabus. So thank you very Have a great afternoon that will see |
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36:36 | on Wednesday. Take care. |
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