all right so um now we're going to discuss the action potential right as we resume our discussion on nerve and muscle physiology and here are our unit objectives so um a quick and brief review here what's the effect of changing sodium or potassium permeability on resting membrane potential so again here is your resting membrane potential here is the equilibrium potential for potassium and all the way on the other side is the equilibrium potential for sodium so what would happen if we make the membrane more permeable to potassium okay and i hope you guessed it right but what's going to happen is the membrane potential is going to move towards ek but if we do the opposite and if we make the membrane potential more permeable to sodium the opposite is true the resting membrane potential is going to move all the way to the other end so um in order for us to talk about depolarize to talk about action potential i'm sorry we need to introduce some terms so minus 90 is our resting membrane potential now and here is zero millivolts so if the membrane potential becomes less negative meaning it's moving towards zero then we call that depolarization so instead of saying the membrane potential increases or decreases use this terminology if it's if you mean closer to zero say depolarization and the opposite is true if it moves further away from zero we call this hyperpolarization now if the membrane potential reaches zero and passes zero into the positive range we call that the overshoot now as the membrane potential decreases again or becomes more negative and moves back towards the resting membrane potential we will call that repolarization and the ability of the membrane to change is its resting membrane potential and basically depolarize and repolarize we call that excitability finally threshold is a certain membrane potential that if the if we cross this membrane potential we're going to generate an action potential right and it's that necessary level that we have to cross in order to generate an action potential and i think this is going to become clearer as we go through this lecture today and you start learning what an action potential is and how it's generated so let's jump into that what's an action potential so an action potential is defined as a regenerating depolarization of membrane potential that propagates along an excitable membrane so an action potential has to propagate right it's going to move down that excitable membrane so propagates means conducted without decrement and it's an active event it's an active event because that's going to be important to distinguish an action potential from electrotonic potentials that we're going to learn about later excitable when we say a membrane or an excitable membrane we mean a membrane that's capable of generating action potentials so here um here we have a nerve accent here we have a stimulator so we're going to stimulate from here and we're going to record from the recording probe there an action potential is going to move in this direction and this is what the recording is going to look like so an action potential has a velocity of about 60 meters per second um which means uh it's gonna cover 60 millimeters in a millisecond right or basically six centimeters this is what an action potential is going to look like you see here we have the equilibrium potential for potassium and here at plus 61 that of sodium okay all right so the first number one here right is we're at resting membrane potential so if you look here there is no action potential yet and the recording electrode is just simply recording the resting membrane potential if we do stimulate this nerve an action potential is going to start moving towards the recording electrode but the recording electrode is still just simply picking up that resting membrane potential now as the action action potential reaches the recording electrode you're going to start seeing that upstroke here because it's going to record a a swift depolarization in the membrane and that's what's going to what you're going to see here at number two and then the action potential as it keeps on moving down the axon right the recording electrode is then going to start noticing a decrease back towards resting membrane potential or what we are going to call a repolarization or the downstroke of the action potential and then finally there's going to be a slight sometimes present sometimes not but a slight after hyper polarization as you see here followed by achievement again of your resting membrane potential now some important basics that i want you to remember that action potentials are all or none events meaning if we reach that threshold we are going to get an action potential and if we don't we're getting nothing either it's an action potential a full incomplete action potential or nothing action potentials have constant amplitude they do not submit meaning if we provide or if we stimulate a nerve um pretty strong that instead of sending one stimulus we're sending 100 the action potential amplitude is always going to be the same yes we're going to have more frequent action potentials but they're all going to have the same amplitude action potentials are initiated by depolarization right as you see of the depolarization of the membrane they're all going to be initiated the same way this depolarization is going to involve changes in membrane permeability and as you can probably guess that you see here that the action potential is moving towards the equilibrium potential of sodium so i'm hoping you can then realize that when we say changes in permeability this is going to have to do with increases in sodium permeability and finally action potentials rely on the voltage-gated ion channels because i think these these all feed into each other so initiated by depolarization which is going to occur by changes in membrane permeability which happens by changes in voltage-gated ion channels so some properties of action potentials again so they're all or non-events meaning if we cross that threshold you're going to get that action potential and what i want to show here in regards to the issue of amplitude so you see here stimulus we provide a stimulus we see a change in membrane potential but it does not reach threshold therefore it just decays and dies out we do not get an action potential we provide a stronger stimulus while the same thing happens but the change in membrane potential is just greater a stronger stimulus here but still we don't see a spike but here we provide a stronger stimulus this stimulus is strong enough to cross the threshold as a result we actually do see an action potential generated we provide a third stimulus here as a result you do get an action potential but note that stimul the stimulus here is actually greater than the one here however the action potentials are the same amplitude and the same thing happens here in this third scenario we provide a stronger stimulus that's stronger than this one and also stronger than this one but yet all of these three ampli action potentials have the same amplitude right and so that's just very important to realize that action potentials are always going to have a constant amplitude an action potential is also going to have a constant conduction velocity for a given fiber however fibers that have larger diameters are going to conduct action potentials much faster than fibers with a smaller diameter myelinated nerve fibers are way way faster as you see here in red much faster in terms of conduction velocity than on unmyelinated fibers and even if you're looking at the myelinated fibers the the greater the diameter the greater the speed of conduction okay so what do voltage-gated channels have to do with this well simply put the membrane potentials remember it's gonna it's all about permeability so looking here at point number one you see this is our starting point the sodium channel which has two gates an activation gate and an inactivation gate at the normal resting state the activation gate is closed shut while the inactivation gate is open this means that the conductance of sodium is very close to zero as you can see here what then happens is that the activation gate opens this increases sodium conductance allowing sodium to rush into the cell initiating the upstroke in the action potential that you see over here now this is then followed by closure of the inactivation gate now what closes the inactivation gate well the same stimulus that opens the activation gate is the responsible for closure of the inactivation gate the only difference is that this second gate is a little bit slower in its mechanics than the activation gate so the very same stimulus that opens up the activation gate will close the inactivation gate and that delay why they're not moving at the same time is just simply because of differences in the mechanics of these gates that cause the inactivation gate to be a little bit slower however when the inactivation gate closes you start seeing that membrane potential moving back towards repolarization or back towards resting membrane potential now if we look at the potassium conductance during resting you see that the potassium channel is closed but that doesn't mean that potassium conductance is zero remember the membrane is much more permeable to potassium during the resting state so you still have some conductance but it's not coming from here it's not coming from these voltage-gated channels the potassium conductance is mainly coming from the potassium leak channels however after a period of time right due to the initial stimulus but due to slow activation as well the potassium channels are going to open when the potassium channels open right as you see here in number two potassium conductance increases even more right than than normal and this also contributes to the repolarization of the resting membrane potential so what's very important to realize here is that the you have a single stimulus right that is going to activate this guy or without using numbers let's just say activate the activation gate close the inactivation gate and open the potassium channel so the same stimulus is going to be responsible for all these changes however they just happen at different times so the action potential summarized again here we have our action potential when the sodium channels open we get that upstroke that quick depolarization and overshoot and this is because of an increase in sodium permeability due to opening of the sodium channels as we mentioned so looking at sodium channels you see that they're going to open and the these channels are going to be responsible for that depolarization that we are going to see okay this is also then followed by the downstroke and the downstroke is going to be due to inactivation of the sodium channels as well as opening of the potassium channels as you see here we can also get the period of after hyper polarization which you see here but it's not always present but um it does it does happen and and that's just a brief period of hyper polarization where the membrane becomes even more negative than it normally is okay so action potential propagation so if this is your nerve fiber and you can see the inside isn't negative relative to the outside you can actually stimulate the nerve right in the middle and when that happens i want you to note that the action potential will actually travel in both directions okay and then you see here it keeps on traveling in both directions until it reaches the um the end where it can no longer propagate the there is a reason though why the action potential does not go backwards and that is because the inactivation gates of sodium when they close they prevent the opening of the sodium channels once again what's important to realize is that the inactivation gates of sodium once they close they will not reopen they will not reopen until the membrane potential reaches resting membrane potential or close to it all right local anesthesia so when this is pretty cool pretty interesting the first local anesthetic used in medical practice was cocaine as you can see here in 1860 and cocaine works by blocking action potentials right if you can block action potentials in nerve fibers you're going to block the uh the sensation of pain but the problem is cocaine tends to have some side effects and so luckily lidocaine was later developed and lidocaine works by binding to the voltage-gated gated sodium channels and making them basically inactive and in order to do this lidocaine cannot gain access from the outside they've they really need to enter the nerve accident first and this explains why when you're using lidocaine active nerve fibers are blocked faster because the gates are open more often allowing lidocaine to actually come in and bind to the voltage-gated channels and inactivating them all right myelination so nerve vaccines please recall that the larger the diameter the faster the speed of conduction myelin also helps with that not just by increasing the diameter but by providing a layer of resistance that makes the propagation of the action potentials and electric current much more efficient in the nerve fibers and what we see is that every one to three millimeters there's going to be a break in the myelin sheath and we're going to call these breaks nodes of ranvier and here you can see a nerve accent and you can see the myelin just being wrapped around that nerve accent and about every one millimeter or so you see a break in the myelin sheath right and this is what's going to be your nodes of ranvier now these nodes are pretty important because right in the middle of the node you're going to have a significant concentration of voltage-gated sodium channels you will have some potassium channels on the sides but it's at the node of raviere where you're going to have a lot of sodium channels concentrated in this location what this allows is for basically the current electric current is going to travel under the myelin sheath just like how copper uh just like how electric current will travel through a copper wire right because of the insulation provided by the myelin sheath we're not going to lose much of that current however at every node of ranvier is going to work as an amplifying station because we have tons of sodium channels so that is where you're going to have an action potential and it's at that site where you're going to generate those action potentials and they're going to serve as uh amplification sites that's why if you when when looking at this from the outside it will appear that the electric current is jumping from one node to the next right or the action potential is going to be jumping from one node to the next and that's why and that's because why that's b i'm sorry that's because of the presence of these sodium channels at the sites of uh the nodes of ram video this observation is called saltatory conduction all right um let's just briefly talk about non-myelinated versus myelinated nerve fibers and so here's a non-myelinated fiber and here's a myelinated fiber and you can see that in order for an action potential to propagate down an unmyelinated fiber it has to move down every single spot right that's how it's going to move from one end to the other however if you have a myelinated nerve fiber where really you only need an action potential to occur at the nodes of ravier it's going to look like that you're not going to need as many action potentials it's going to appear that it's jumping from one node to the next what we call saltatory conduction and the speed of conduction therefore is going to be much much faster so when thinking about a disease like multiple sclerosis which is an autoimmune disease that what happens here is demyelinating or demyelination inside the central nervous system and so normally you would have your regular myelin sheath but then as you start losing parts of that myelination um when an action potential tries to be prop or to move and be propagated down because you lost that myelin sheath and because you have the concentration of sodium channels at the nodes of ranvier by losing that myelin sheath you're no longer able to propagate an action potential down the nerves and therefore patients are going to start experiencing signs and symptoms of this disease here's a question for you um i'm going to let you read and answer this question on your own feel free to pause the video and with that we end this lecture thank you so much and see you next time