in talking about graded potentials we mentioned that a stimulus can cause a small deflection or a small change in membrane potential in this case we show a green arrow indicating this is an excitatory stimulus and notice that that is then going to cause a small depolarization the green line in this picture represents sodium's equilibrium potential the purple dashed line represents potassium's equilibrium potential this blue dashed line that I've included here represents something we call threshold so if a stimulus can change can cause a change in membrane potential such that it reaches this threshold then at this point a new type of channel is opened so if we have a larger stimulus that gets us the threshold this new channel will open and this new type of channel is called a voltage-gated channel because it is at this voltage that will cause the opening of the gate that will allow ions to then move so in talking about graded potentials we said that the next thing that we'll talk about is an action potential and that's really the function of a graded potential is can it get its to a point that we can generate an action potential so Action potentials are going to be generated when a graded potential brings a membrane potential to threshold so once we reach this threshold voltage then an action potential will follow and you'll notice that an action potential is very large in comparison to a graded potential recall that our equilibrium potential for potassium is at minus 90 or 92 and sodiums is at Plus 60. so knowing that this is these ions equilibrium potentials it should give us a good idea of what's happening with this depolarization as well as what channels are involved with the repolarization so the voltage-gated sodium channels are quite interesting they have two different Gates they have an activation gate and they have an inactivation gate so in order for sodium to move we have to have both of these Gates have to be opened so what happens at threshold is is that once we reach threshold threshold causes this activation gate to open and that now will allow sodium to move in as sodium moves in the cell's membrane potential starts to move toward sodium's equilibrium potential now after this voltage-gated sodium channel is opened there's something about it that causes it to then go through another conformational change that's about a millisecond later in one millisecond after it opens the inactivation gate then closes so notice that when this is closed no more sodium can enter and that's what causes us to peek out at this millivoltage with an action potential so the voltage-gated sodium channel can come in three different conformations we have our starting conformation and this is called closed but capable of opening it's capable of opening if we reach threshold so once we reach threshold that's going to activate this Channel and cause the activation gate to open notice that this can only move in this direction we can't go straight from this conformation backwards a millisecond after this channel has opened the inactivation gate then closes so now we refer to this channel as closed and incapable of opening so no matter what we do to it at this point we can't get it to go backwards in this confirmation we refer to this as being inactivated and then as this recovers it will then go back to its closed but capable of opening State and this occurs when the cell goes back to the cell's resting membrane potential now when threshold voltage is reached we also have another type of voltage-gated Channel That's opened and this is called a voltage-gated calcium potassium Channel so this channel is activated at the same time as the voltage-gated sodium channel the difference is is that the voltage-gated potassium channels are much slower to open as well as slower to close so we don't see their impact initially when these voltage-gated potassium channels open they are going to allow potassium to move out of the cell so here we have a cell which has become more permeable to potassium and we know that as we make a cell more permeable to an ion it's going to cause that cell to move toward that ion's equilibrium potential which in the case of potassium is minus 90. so when we start to see those effects of potassium moving we're going to see that that's going to be driving repolarization now these channels are slow to close as well as slow to open so because they're slow to close potassium continues to leave the cell and therefore we become hyper polarized before returning back to normal back to our resting membrane potential so here's a graph which shows the different conductance of these ions over time notice that once threshold is reached both sodium and potassium channels are opened but because the sodium samples channels are much more rapid open we see their effect much more readily and that's what is driving the depolarization once those close we then see the effects of potassium and that's what drives the repolarization notice that we have this period of hyperpolarization because those potassium channels are slow to close now what eventually gets us back to resting membrane potential is the fact that in this case potassium is leaving the cell and that's what makes the cell more negative but with the actions of the sodium potassium pump as well as just our normal potassium leak channels eventually that's going to equilibrate things back out at our resting membrane potential of -70. now action potentials as opposed to graded potentials are going to have some of their own characteristics Action potentials are going to be driven by time dependent changes in voltage-gated channels so this time dependent changes meaning sodium opens up quickly in first potassium opens up slowly in second action potentials are all or none meaning that as opposed to Greater potentials which we could see different sizes and action potential is always the same size for a particular tissue type because it's always the same size it's always excitatory meaning it always will depolarize because it's always all or none it's always the same size this means that his Action potentials are propagated they do not weaken they will always travel in One Direction and this is going to be related to the fact that they cannot summate and again the summation if they summate it that means we would have a larger action potential and we've already established the fact that action potentials are always the same in a particular tissue so let's once again just review the confirmation of the voltage-gated sodium channels during the action potential at resting membrane potential we are closed but capable of opening once we reach threshold we then are open and sodium is moving in and that's what's driving the depolarization a millisecond later the inactivation gate closes and that's what's going to then cause us to max out at around positive 30 millivolts and then the repolarization is happening driven by voltage-gated potassium channels and then once we get back to resting membrane potential at -70 we're then going to get back to our initial closed but capable of opening state with regards to the voltage-gated sodium Channel now with the voltage-gated Sodium Channel we refer to it as having refractory periods so let's work through this so here's our different confirmations of the voltage-gated sodium Channel remember that for summation to occur we'd have to have additional flow of sodium into the cell and we've said that we cannot have summation of action potentials the reason we can't have summation is because of the fact of these refractory periods so we have something called the absolute refractory period and the absolute refractory period encompasses the time where absolutely no stimulus nothing can bring about a new action potential so this is going to correspond to this phase of the action potential which encompasses most of it so correlate what we've highlighted here to what phase or confirmation the voltage-gated sodium channels are in this is going to include the open or active phase so this is going to correspond with the depolarization phase so realize when this is open and active we can have no more additional sodium entering we've already kind of maxed out the amount of sodium that's moving a millisecond later we max out at our voltage around positive 30 and this is when the inactivation gate is closed and incapable of opening so there's nothing we can do during this phase to get this to open to allow more sodium in so both of these conformations correspond to the absolute refractory period the relative refractory period is a time when a stronger than normal stimulus may result in an action potential and that's going to correspond with this phase of the hyperpolarization where we're more negative than where we started so that's going to correlate to the closed but capable of opening state so whereas here we just needed a graded potential to get us from minus 70 to -55 here we'd need a stronger graded potential to get a say from minus 75 up to threshold so these refractory periods prevent us from summating but they're also responsible for the unidirectional propagation of action potentials so Action potentials are only going to travel in One Direction along a nerve so this is a very simplified diagram of a nerve here's our cell body this is the axon we have at the beginning of the axon an area called the axon hillock or trigger Zone and this is where we have a increased density of voltage-gated sodium channels so what we're going to see happening is is we're going to see this is going to be where if we reach threshold in this area we will generate an action potential that action potential isn't going to send its electrical signal down the Axon this voltage from this action potential will then cause the portion of the nerve here to reach threshold and that will cause the opening of voltage-gated sodium channels generating another action potential this action potential is going to have its electrical signal sent in both directions but notice as it's moving backwards it's hitting a part of the neuron that is in the absolute refractory period therefore this will go no further going forward it then is going to generate another action potential and that action potential is going to send its voltage in both directions but again as we move backwards we're going to be running into the absolute refractory period which means we can't generate an action potential there but we continue to move this forward