So, how do they describe the electrical circuit in the membrane. Well, through their study, again we will discuss in detail, they describe the membrane of a neural cell initially. But now can be generalize to any neurons. Including our brain, the neuron in our brain, into the circuits like that. There is in across the membrane Okay? This is the membrane. That the membrane is. Has one capacitor, the membrane capacitance, the capacitor, okay? That takes time to charge, okay? But at the same time, near this membrane there is batteries. What is the battery? In fact, the battery, this is just the membrane potential, or the equilibrium membrane potential that it would describe for potassium. So when these potassium ions are conducting, when this circuit is on, then the battery's potential is the resting membrane potential, or the driving force for this potassium ion. Because only under this condition the potassium ions will not be moving. So this is the potassium battery. Likewise if there is sodium channels allow sodium go through and when the sodium channel is on the battery of the sodium will be on, okay? And for chloride, okay? So essentially the membrane can be simplified into three components, with permeability on the battery charge with different sides potassium, fluoride, sodium and the capacitor in parallel. All of this battery that will generate current is eventually going to charge the- capacitor in the [INAUDIBLE]. Okay, and it's this simplified diagram that today derived in 1952. Okay? Classical general physiology paper that lead to our fundamental understanding of the action potential and the of the potassium channel, sodium channel, chloride channel. And think about it. We have this membrane potential here. And if we study the membrane potentials Relevance to sodium conductance, potassium conductance, we are essentially trying to study how the conductivity, or the permeability of a sodium according to the membrane potential. As we will note the excitable cells have a special machinery that can sense the membrane potential, and then will open or close to allow specific ions to go through. And this ion goes through, will also in turn change the membrane potential because they are going to charge the membrane capacitor. So you have this complicated relationship that you have the channel will respond to membrane potential. And then it opens or closes when we will change the membrane potential again. And indeed this complicated relationship can be modelled by the computer. And indeed, using the computer to probably generate the first computational neuroscience study that is the generation of action potential using the magic parameter, and using the [INAUDIBLE] computer, okay? So they have this classical theory of papers describe almost everything, okay? So let's look at the neurons' passive property. That is that property for capacitance resistance and the battery. Okay? Without this special conductance that on the iron channel that will be regulated by the membrane potential. Okay? So if we do this experiment again, in the synapse. Okay? A classical preparation That lead to many Nobel prizes. Okay. essentially, the screen axon is the perfect robust cell just as the one I draw. Okay? You can do many electrical signals. Recordings you can change the ionic concentrations. Yet it's still robust in respond even after doing recording for 2 hours. Okay, so if you do such a let's see okay, it's a this is a Axum and then we insert electrode to it. So for example, we can insert electrode to it, and then we can deliver the current, we can inject the current by one electrode. And we have another electrode in the close region to measure the membrane potential that is the voltage change for in responding to the current injection. What we observe is that if we inject a unitary or rectangular current. That is, the constant current here, what we observe is that the voltage change is as if it's a capacitor that initially the [INAUDIBLE] does not instant tendency goes up to the fixed value. Rather it takes time to charge the capacitor and then once it charge it eventually it charges to the such a reaching point, the membrane potential will no longer goes up. Okay. And then if we start the current that's no longer the current injection, the membrane potential is continuously goes down. But rather, it takes time to decay. So this are a property of the capacitor that it takes time to charge and it takes time to discharge. So that in the case of the membrane has this capacitor. And if you have a lot of axons then those capacitors are in carrier configuration. They all have this unitary capacitance okay. Because you can do those experiments, for example you record the only in adjacent region. But you record in a little bit far away. And even far away, what I observe is that the membrane potential will decay. Rather than it goes to this level, it just decayed over time, okay. So this reflects the current that goes away from the resistance. And therefore, over distance the amount of current actually also get decayed. And then it charge the membrane potential to a less amount. And there are more capacitance over this region. Now the voltage can be described by a combination of the different resistance. For example, the resistance that allowed the membrane current to go through. So this is the membrane resistance or this is the actual resistance our I that is the resistance of that go in serial along the axons. And the net effect is the current will goes down with the, the current charge of the membrane will goes down. And then the membrane potential, if you charge your single point. And you measure all the membrane potential according to a distance. The membrane potential at far away will be lower and lower and lower. Those are just the cable theory, the cable property of the axum. And those does not require active Ion channel. Any cable can do that. But if we are doing more interesting experiments in the axon, that is we inject different colors. And here's the interesting one. We can Inject current with different direction, for example, the current to hyperpolarize the membrane. And we can inject different amount, okay? And where you observe, interestingly, this is the property okay? For example, if we inject hyperpolarizing current. Okay, and you observe a passive property you are charging a capacitor in a different direction. And then discharging if you are inject less current then it goes there less and then comes back. And if you inject the current in a different direction Initially things are still not so interesting. It seems to be just a sort of a mirror imaging of this current. But if you increase the amount of current injecting, there is something interesting to happen. There is you certainly seen it there is something here and here there is actually action potential after this. And if you inject more current what you observe is that always there is action potential. Okay? And this is an interesting for this active process. So, rather than is just the reiterate image of all those things, the cell actually will generate action potentials. And, as you can see, if we inject the current d tour voltage just right at the threshold. Sometimes you'll get an action potential, and sometimes you'll fail to get an action potential and the current goes down. Okay? In fact, even the property of getting action potential is at 50%, people define this as that is the threshold. 50% to get action potential. To present it goes back, back to the baseline, or resting membrane potential. Okay, and again, the experiment like that demonstrating there is an active process for the membrane potential, why? If you still remember, at the beginning we talked about Bernstein, the German scientist in 1990s. He proposed correctly the membrane potential the rest potential is determine by potassium. and he also proposed that during the action potential the membrane breaked up, and the membrane potential will increase Okay. He's a genius. Even though he's not totally correct, but he's mostly correct because what you observe is during the action potential the memory potential goes up to about 35. Okay? So indeed, the number of transportation changes and is some process requires because of the changing of the selectivity, changing of the conductance. Of okay? Why? Because even without the membrane potential changing induced by the current injection if you look at here, okay. The current injection is right at this point, okay? But after you stop in this, you generate an action potential a little bit later. There is no longer a current injection. But, you have a real voltage there is a 30 million volt. Very different than the resting membrane potential. Okay? They're indicating something, why? Because we've already spent the whole day or the whole lecture discussing that the ion channel, or ions concentration and its permeability determines the membrane potential, okay? In a resting condition is the potassium determine the [INAUDIBLE] potential minus 70 minimal okay. Here we route our extra current injection you got a variety for membrane potential which is a plus 30 millivolt right? So this indicates that if we have membrane potential it is determined by the ions, it got to be some different ion. Okay. Because if it is protacide then it's going to be minus 70. Everybody with me? And especially you don't inject any current into here you are artificially injecting current and less changes. Can be understood by this current ingestion that passive property for charging the capacitor. But this active process here after this active process that if we reach the threshold, this is not due to the current injection alone. Okay,because current injection alone is going to produce this passive property that can be easily to describe by the capacitor and resistance. Okay. So this, indicates this is some going on. And if you are going to bet your money, it's going to be alteration of Ion probability, and most likely is not due to potassium. Then what ions that will control this change of probability? What ions? Sodium or chloride right? Because in our condition we only put these two ions then how do you know which one is playing an important role. As you said just changing the ions concentration If the i is a permeable and determine the voltage. Then you change that concentration according to the equation that we spent half of the class to derive. Then it's going to change the driving force. It's going to change that peak. So in the next session that we are going to discuss is the heroic work of Huxley exactly doing the experiment by measuring the voltage and then changing the ionic concentration. And then to test Which one determines the peak and which one will make it go down. Okay. And pseudo's experiment and detailed quantity measurement they conclude is indeed sodium that drive the membrane potential to the plus 35 millivolt and then they at this voltage. It will activate another [INAUDIBLE] ion channel which is potassium permeable. Then you will drive [INAUDIBLE] goes back to the resting state, and this interplay of these two ion channel that generates this interesting [INAUDIBLE] substrate. Okay.
