All right, let's start with a cell, okay? We have a way, using an amplifier, to amplify small voltage signals to record those cell membrane potentials. And then we generate this apparatus that through this fine electrical or class electrical we can insert into a cell to measure a cell's electrical property. For example, if the electrical is fine enough that you can insert into the cell without disrupting cell's property, and we can measure the voltage from the cell. Magically, when you measure that, the voltage is frequently -80 mV, or -70 mV. In fact, historically people have done that and then imagine, they call it a funny name. Okay, they call it a funny name as angel potential. Okay, as if [FOREIGN] They got not human potential. They don't understand why this is such an active membrane potential to the cell. They some how injure this cell and then you get a potential so they call you injured potential. And interestingly the most skillful people trying to make this recording a subsequent found. If you put in more fine tips most likely will not injure the cell that you got more negative okay? Close to -18 [INAUDIBLE] if you make a pretty big [INAUDIBLE] okay. Then sometimes the membrane potential would be -40 millivolt. People doesn't understand why there's such a membrane potential, okay? Well, since we have in the modern days we have some physics background, right? Then when you have a different member potential, in this case, we count the internal side of the cell, zero which is a ground. And so you get a ground, okay? Inside, it's a -18 meter roll. That indicates that there must be a charter separation, okay?. There's more negatively charge inside the cell comparing with outside the cell, okay? So why this is the case? Why the opia negatively charge inside the cells, okay. This actually is because of the different concentration of the ions in the interior. Was the outerior of the cell, okay. we have a different iron concentration irons having the different amount of charge, and then they will have different charges separation okay. So for example, what is the charge of potassium? Plus one. The charge for a potassium ion will be plus one. What will be the charge of? Class one. >> Class one. >> Minus one. >> Minus one, right, chloride. Right? And what is the charge of calcium ion? >> Class two. >> Class two, okay. So If one people measuring those different ions and their concentration for a typical self. You can see that the chart ends the concentration is different. Okay, an active charged chloride, positive charged potassium but for a typical cell. Usually what you'll find is that the inside of the cell has a higher concentration of potassium, lower concentration of a sodium, okay. And outside of the cell has a higher concentration of sodium, lower concentration of potassium, okay? But does that sufficient to its brain? The, a lot of, memory potential that you record. Okay, why the memory potential -80 millivolts rather than -40? Okay what determines the [INAUDIBLE] member potential meaning that there's no such a action potential generation it just possibly recall the cell. What determines it is determine by sodium, potassium chloride or, maybe there some additional ions, and then they have different distribution. Maybe the will determine the memory potential and the resting memory potential. What is the quantitive relationship between the ionic concentration and the memory potential, okay. Let's, what do you guys think, okay? First let me just ask, looking at this image is chloride determine the memory potential, chloride. Okay, because outside the cell, there's a lower concentration of chloride. Outside of the cell there's more concentration of chloride. If chloride Is the determinant of the membrane potential. That the membrane potential will be what? Will be positive, right? Will not be negative, okay? Right? Okay? Then we can think about the sensing for sodium and potassium. Let's just do one-by-one. If sodium is the main determinant of the memory potential. Will the memory potential be minus 18? See, sodium has a less concentration positive. Less positive concentration inside. Outside it's higher. So at least the the sign is consistent with the membrane potential. Low inside, right? How about potassium? How about potassium? So likewise, potassium has a higher concentration inside, right? And lower concentration outside in potassium determines here. Do the synthesis interface, no. Okay as you guys will see since my [INAUDIBLE] I'm expected okay. So The story starts from 1990s-ish. Bernstein, a great German scientist, he proposed that excitable cells are, they are resting membrane potential, are determined by the potassium concentration, okay. Big surprise, okay. And he even proposed the mechanism of action potential, okay, as we will discuss in detail later. He said the action potential how you generate because in the 19th century, people can already use the electro physiology recording outside of the cell. It's called external recording to detect the generation of action potential. And then That he proposed that dealing the action potentials, this selectivity for potassium get transiently lost. And he membrane are permeable to other ions. So he proposed that how to the action potential is generated is, in a resting condition is permeable to potassium and during action potential somehow the membrane breakdown. And then all eyes can freely pass in that case the membrane potential will be 0 medieval. As we also discussed, and this is the mechanism of action potential, okay? He might not be right of the total membrane breakdown in this case but at least, he's correct in the sense that he proposed that [INAUDIBLE] determines the [INAUDIBLE] of a potential okay. So how do we do that is [INAUDIBLE] to demonstrate rather the potassium is a important determinate of memory potential. Well, you can do the experiment, okay start with our sort experiment. If you have a very skilled head, and you can recall your cell, okay and what you can do is since you want to test potassium determines the membrane potential. All you can do is to disrupt or altering the potassium concentration, right? And then you match it what has changed of the memory potential. So in this case, if we do that spot experiment, we into the cellular memory potential. And then superfusion, or changing the internal ionic concentration, you first change the sodium. And then we thought that it doesn't matter what concentration of the sodium we use. That's essentially not too much a difference of the membrane potential, okay? So you say, maybe I don't know the reason but if I change in the sodium, the membrane potential does not change. So it's unlikely as it is the outside sodium concentration will control or will determine the memory potential. But if you do so for example within a cell, if the cell is long leaf cell, right. Very skillful the cell that goes through all the tortures that you have to change the solution It's still there, okay? Then you change the potassium concentration, and what do you find? Ha, ha! If you change the potassium concentration, actually the memory potential recall changes. Okay? If you are not so skillful, well you can recall at least two cell looks identical, right? You choose two sister cells, okay? Or you choose a group of cells. You do 10 cells with 1, condition and you do 10 cells with other conditions and that can give you a simple of what's going on for the group cells, okay? And then [INAUDIBLE] when you generate host that will you change in the potassium will auto [INAUDIBLE]