Transcript for:
Action Potential Lecture

all right so we've talked about the resting potential uh the forces that govern how it is a neuron is able to stay in an inactive State when it's not being acted upon by other things and now we're going to talk about the opposite of that the action potential how is it that the neuron is stimulated or brought out of that state of rest so that it can transmit a message to another neuron we're going to break this up into two different parts because it can get a little bit heavy at times so I don't want anybody to sorry I don't want anybody to get overwhelmed um and uh and yes so we'll take a little bit slow here break it into two so goals for this lecture uh we are going to talk about ion channels again this time we're really going to zoom in and focus on our uh Volt or our sodium channels in particular and we'll really focus on voltage-gated sodium channels um and then we're going to talk about two different types of potentials epsps and ipsps which stands for excitatory postsynaptic potential and inhibitory postsynaptic potential both of these are things that are messages which can influence the neuron in One Direction or the other and make it more or less likely that an action potential will occur all right so let's go over some basic vocabulary here uh we talked about the membrane and we said that at rest the membrane is typically on average resting around negative 65 millivolts when the membrane moves away from negative 65 millivolts into the positive direction we call this depolarization of the membrane so depolarization of the membrane is when the membrane potential the inside of the neuron Etc is becoming more positive okay more positive now this might sound confusing but in terms of physiology the physics that is referred to as a reduction in membrane potential why is it referred to as a reduction in membrane potential well we said that the difference in charge between the inside of the neuron and the outside the extracellular fluid of the neuron the bigger that difference is the more potential that there is right that's the the charge the More Voltage right necessarily and so the inside of the neg of the neuron is really negatively charged it's filled with negatively charged proteins the outside of the neuron is really positively charged it's got lots of sodium floating around and very little negative proteins and so there's a big difference between those two and therefore there's a lot of membrane potential right when the neuron depolarizes it becomes more positive well hey guess what the outside of the neuron is also positive so there's less of a difference between them and so therefore there is a reduction in membrane potential okay now for your purposes though as a student of you know introduction of Neuroscience the easiest way to think about this is to just think that depolarization means that the neuron that number that membrane potential number is going to move more towards the positive direction so it's at rest around negative 65 and it'll go up to negative 45 negative 40 even into the positive direction eventually it's moving away from the negative okay next thing that's important here okay the threshold the threshold potential the threshold potential is the measurement in millivolts at which if the neuron crosses this point an action potential will occur you can't stop it from happening an action potential will occur we're gonna talk about what an action potential is here in a moment now the threshold potential is typically we give an average at this point in the course and we'll say it's around negative 40 millivolts some sources might say negative 50 millivolts that's fine okay that's fine too just know that basically it's a number around that between negative 40 to negative 50. that if you cross it if you go to say I don't know uh 30 neg 35 you've crossed threshold an action potential is going to occur um and remember we said that at rest a neuron is typically fluctuating between negative 50 to negative 80 millivolts note that I said between neg 50 to neg 80. I didn't say neg 45 to neg 80 neg 40 negative right if it crosses that point it's crossing the threshold okay other key points here voltage-gated sodium channels so they are voltage-gated which means that the voltage when the voltage raises to a certain point it's going to cause them to open and when voltage dips below a certain point it's going to cause them to close um when voltage-gated sodium channels open on the neuron there's very little sodium inside the cell the sodium the inside of the cell is negatively charged the outside is positively charged electrostatic pressure is going to want to bring sodium into the cell that's going to raise the membrane um that is going to depolarize rather see I almost made a mistake there myself it's going to depolarize the membrane right gonna make it more positive then we also have voltage-gated potassium channels in the last lecture we focused on leak potassium channels today we're going to focus on voltage-gated potassium channels once again these are potassium channels that are going to open in response to depolarization of the neuron so the positivity or that voltage is going to raise to a certain point that's going to trigger opening a voltage-gated sodium or potassium channels and then when it dips below a certain point they'll close back up okay so let's continue our focus on voltage-gated sodium channels we're going to break them down into their constituent components if you take a look in the lower right image here are two major parts to the voltage-gated sodium Channel and remember we said that in general um these are Gates right they're channels okay uh they open up and they are going to allow the flow of sodium through there's two parts to the gate okay there is an M gate and an H gate the M gate is the activation gate so when voltage raises up uh on the neuron in a sufficient to a sufficient quantity um voltage-gated sodium channels will begin to open the M gate is activated okay it's a fast movement M gate is fast so typically around uh negative 40 millivolts here we can see this definitely at negative 40. um we can see here here's our resting potential neg65 a current is injected it raises the potential to or I'm sorry it depolarizes the neuron to around negative 40. and okay what here's what happens uh M Gates activate really quickly there is an inward current a flow of sodium in okay and as that flow is coming in the voltage is rising Rising rising Rising rising and it's going to get up to a certain point when it gets uh and then ultimately that flow is going to stop because there's a ton of sodium inside the neuron right it's going to stop flowing in you can't let any more in and this whole time the H gate is working very slowly so the M gate is what opens the channel and once the channel is open the H gate is slowly working and closing the channel back up so this ensures that the voltage-gated sodium channels it's like they're on a timer okay the voltage raises up it causes them to Spring open and then there's a timer and it's slowly closing the door closing the door closing the door right uh so it's like they're on a timer and the timer tends to coincide with we're going to find action potentials our very brief blips changes in membrane potential very brief blips where the membrane depolarizes and goes up up into the deposit and that drops way back down into the negative and that timer tends to coincide so you'll get sodium channels open up fast in response to increasing voltage and then they begin to close and the neuron begins to move back down we'll go through that together here in a little bit just know for now the difference between the M gate and the H gate activation inactivation so voltage-gated sodium channels just like our potassium channels I would say are some of the most important components of the neuron and if you disrupt their function you will disrupt the functioning of the nervous system and it could potentially cause death so uh we talked about in the previous lecture scorpion toxin scorpion toxin blocks potassium channels we talked about how that will just cause the membrane to depolarize depolarize depolarize because it disrupts the ability to remain at rest uh and then we mentioned briefly that you know toxins which block voltage-gated sodium channels kind of have the opposite effect now the neuron can't leave the state of rest okay why is this relevant well here's an example of from sushi restaurants what's often called Fugu f-u-g-u um Fugu is another name for puffer fish and puffer fish have a toxin which is concentrated in certain parts of their body I believe in the liver some other spots and that toxin uh blocks voltage-gated sodium channels so you're unable to send signals unable to send messages so uh people will prepare Sushi made of fugu you have to have a special license to do it because it requires a very very uh good knowledge of the anatomy of the fish so that you don't get the poison into the sushi um but if a mistake is made it could be pretty problematic it could cause somebody to die right uh if you're unable to send signals via voltage-gated sodium channels unable to send uh uh chemical messages that is going to lead to paralysis it'll lead to paralysis of the lungs the heart Etc and so uh this is a common thing when talking about uh toxins that that affect different channels in them so that particular toxin from the puffer fish or from Fugu is referred to as TTX or tetrototoxin and as I said it blocks voltage-gated sodium channels there are other toxins which also block uh these channels as well saxotoxin or STX generated from dinoflagellates it's what is contained in the red tide blooms uh and so it's just another example of a way that organisms animals have have evolved mechanisms uh with which to prevent them from being preyed upon really um and and interact with other nervous systems the the evolution of toxins is really just a fascinating concept to consider and sort of this terms of like an evolutionary arms race um that said TTX STX very useful in a laboratory setting when you are interested in neurophysiology and you're and you're interested in the properties of the membrane and electricity and flow of current right and you can selectively block sodium Channels with these chemicals so you do see them in use in Laboratories that are doing that kind of work but you also see um a selective use of things that block voltage-gated sodium channels in the medical industry lidocaine for instance lidocaine typically that suffix cane is denoting a a drug that is a drug that is um blocking pain signaling in some way a local anesthetic okay uh a local anesthetic means that you apply it to an area and it numbs the area it prevents pain transmission from a very specific small local area of body lidocaine does this by specifically blocking binding with the poor Loop for sodium channels the S6 poor Loop there's several poor Loops for sodium channels it blocks and binds with the S6 poor Loop in particular and blocks sodium flow okay this when you inject it into an area prevents the neurons in that area which sends signals related to pain transmission from setting those signals up to the brain okay lidocaine great example of this there are other examples too see if you can think of a few if you pause the video for a moment one of the examples that I'll give would be novocaine novocaine used in the dental industry another uh local anesthetic that works through a similar mechanism and cocaine cocaine was originally used in surgical practice in dentistry for the same thing right if you rub cocaine on the gums it leads to a numbing sensation Believe It or Not cocaine actually does block voltage-gated sodium channels to a certain degree that's not the mechanism by which it gets an individual High that's a different conversation we'll talk about that later in the course but in terms of why it causes a numbing sensation why it was used for that similar mechanism here okay other toxins uh that are interesting to consider but trachotoxin this is located in dart frogs okay poison dart frogs in there is secreted from their skin okay there are also some beetles and some birds interestingly enough uh that that secrete this toxin as well and in particular um The Beetles that secrete it they're from this genus called corosine the birds that eat those beetles that's why they wind up secreting the toxin themselves similar to how the poison dart frog winds up secreting the toxin due to its diet as well uh so that's betrayco toxin there is uh veratine uh another substance here coming from flowers this one is a little bit different so what it does is it causes voltage-gated sodium channels to open up and remain open for a long period of Time same thing with the tracheotoxin it does this as well causes them to open up and stay open that's a problem right for regulating membrane potential we already mentioned scorpion toxin how it interacts with potassium channels but some of these toxins from scorpions also interact with sodium channels as well and what they do is they don't block the channel they do block potassium channels but they don't block the sodium Channel instead what they do is block the H gate from doing its job so they block the sodium channel from closing by blocking the H gate let's review our ionic concentrations and let's add some more into that diagram that we used in the last lecture recall that the inside of the cell is characterized by a large number of negatively charged proteins the outside is characterized by a small number or none in terms of negatively charged proteins the outside of the cell has a whole lot of positively charged sodium ions the inside has very little the inside of the cell has a whole lot of positively charged potassium ions the outside has very little and then now we're going to talk about a couple of other things chloride negatively charged ion there's a good deal of chloride outside the cell not enough to overwhelm the amount of positivity out there right we've still got plenty of sodium a little bit of potassium and some other things too calcium here but there is some chloride floating around which is negatively charged inside the cell usually there's small amounts of chloride but we'll find again later when we talk about neurotransmitter systems certain channels will open up and allow chloride in in order to inhibit a neuron or to quiet it down those are called gabaergic receptors and they open up to allow chloride in calcium positively charged there is a little bit of calcium outside the cell and there's a little bit of calcium inside the cell which is being stored in areas that can be released in response to certain stimuli calcium we'll find is super important when it comes to different intracellular signaling processes and kind of kick-starting chain events so that's updating our distribution a little bit there let's see how these things change uh in relationship to the action potential well first let's describe what an action potential is okay and what it is not an action potential is a brief very brief change in the membrane potential of the neuron in the positive direction we call that depolarization okay the the in in terms of physics the polarity of the membrane flips okay it flips in the positive direction from the negative um so an action potential is a brief change in polarization of the membrane and it is characterized by let's look at this middle figure here this for this one characterized by a movement of the neuron out of the resting state which we say is around say negative 65. uh briefly and and sharply up into the positive up into the positive maybe up to like plus 40 or so so you see this pattern in which it shoots up and then it rapidly drops back down it drops down below the resting state and then it kind of returns to its average of around next 65. so the neuron becomes more positive If It Moves In the positive direction briefly and it's what we call an all or none response and all or none response what that means is that you can't have half of an action potential right an action potential either happens or it doesn't it goes up to a certain point and then it goes back down to a certain point there's no such thing as half of an action potential and this is because if you cross the threshold for a neuron say egg 40 on 845 or so it's good that threshold is going to differ from neuron to neuron but it's usually between neg 40 and egg 50. let's say it's neg 40 here if you cross that threshold this is going to happen you're going to shoot all the way up to like say plus 40 and then drop back down you're not only going to shoot up to say plus 10 plus 20 you're always going to shoot up to say plus 40. it's always the same and it happens and then it's over with Okay so one of the ways that we can illustrate this concept this concept of all or none is the idea that increasing the amount of current let's say let's say that you've got a neuron and you've isolated it in a dish of of cerebral spinal fluid okay you've got a recording electrode no reference electrode so you're recording changes in voltage of the neuron then you take another electrode and you stick it in and this electrode allows you to inject current into the neuron okay so let's say you apply a depolarizing current to the neuron okay positive voltage increase no matter how much voltage you apply as long as the voltage is sufficient across threshold threshold and action potential will occur but you're not going to get an action potential that's bigger than one action potential if you apply more current what you will get is more action potentials so take a look here we've applied um a little bit of current just enough to cause an action potential and then we reduce the current okay here we apply a really strong amount of current what happens you get four or five Action potentials in a row blip blip blip Flip Flip just like that what you're not seeing is a difference in size they're all the same size okay so this is what that's illustrating an action potential is the same every time once you cross threshold it's all or none it's gonna happen if you inject more current it just means you're going to probably get more action potentials within a short space of time so what is happening at this point right well the action potential is literally the flow of electricity from the membrane around the Soma of the cell it's flowing around the membrane and it's moving it's charge positive charge moving around the membrane down the axon flowing down down until it gets to the terminal output region the terminal Bhutan and it's going to trigger the release of neurotransmitter from that neuron to send a message to another neuron that is the purpose of the action potential so let's take a look at uh the distribution of channels in the in the neurons membrane we're going to focus here again just on sodium and potassium channels but let's take a look at what these channels are doing throughout the process of the action potential so remember here where it rests say around neg 60 next 60 millivolts first off let's remember that we said that at rest the majority of channels in the neurons membrane are closed okay you've got a few uh leak potassium channels which are open say these here but the rest of the channels in the membrane are closed so you've got open leak potassium channels but closed voltage-gated potassium sodium channels and closed voltage-gated potassium channels now what happens some sort of stimulus is applied to the neuron okay an epsp an excitatory postsynaptic potential and excitatory message is sent to this neuron and it causes the neurons potential that it causes it causes the neuron to depolarize okay causes the voltage to move in the positive direction slightly okay so let's look here as the voltage goes up up up up up and it gets to threshold in this case negative 40 millivolts threshold is met and then all of a sudden these voltage-gated sodium channels pop open they click open super fast now what's gonna happen well the inside of the neuron is still overwhelmingly negatively charged it's at neg 40 millivolts relative to the outside there's very little sodium in the neuron so what's going to happen you open those voltage-gated sodium channels and it's negative inside positive outside positively charged ions are going to want to rush in okay so sodium ions rush in that causes a rapid rise in the voltage okay towards the positive direction so this kind of happens as like a chain reaction you start to get opening of these channels opening opening opening opening until all of them are open and when all of the voltage-gated sodium channels are open that's when you hit your Peak okay this is why the peak of the action potential is always the same in this image it looks to be about plus 40 millivolts so you get to your Peak and the peak is mediated by the fact that now all the voltage-gated sodium channels are open all the sodium that's going to flow in has already flowed in you can't get more positive at this point now something else has to happen what happens now we're in this blue period here and I'm going to cover some other aspects of this momentarily now is that the voltage-gated potassium channels are going to open see this here on this part voltage-gated potassium channels open why is that relevant well okay we're at say plus 40 millivolts that triggers the voltage-gated potassium channels to open and we say that inside of the cell at any given time there's usually more potassium lots of potassium than there is outside there's always these leak potassium channels which are open and a little bit of potassium will leave but it's leaving slowly and the voltage and then the sodium potassium pump is still bringing potassium back into um to keep it at an equilibrium right well how about now voltage-gated potassium channels open a whole bunch of them they click open now the membrane is way more permeable to potassium than it was you've got a ton of potassium in the cell what's potassium going to want to do it's going to want to leave down its concentration gradient so it's going to rush out of the cell so right around here we get to the peak of the action potential all the voltage-gated sodium channels are open there's as much sodium as you can fit in there so more sodium doesn't want to enter and now the voltage-gated potassium channels click open there's already a lot of potassium in there and it wants to leave so what does it do it rushes out of the cell and this as it's rushing out of the cell causes the membrane potential to move back towards the negative direction we're proceeding downward as we move back towards the negative direction that is going to cause the voltage-gated sodium channels to close back up as well so the voltage-gated sodium channels close tons of potassium has rushed out of the cell and that gets us down to here what we call the after potential this is a point in which the neuron is so negatively charged it is actually below resting say around negative 80 or so and it's way down there it's way negatively charged the voltage-gated sodium channels are closed now the voltage-gated potassium channels clip closed as well and now the only channels you have open are leak potassium channels but hey there's not much potassium in the cell so the leak potassium channels aren't allowing any potassium to leave the cell but what's going to happen so some potassium will begin to enter back into the cell through the leaked potassium channels and through the actions of the sodium potassium pump which is constantly bringing back two potassium ions in for every three potassium or sodium ions it kicks out so that coupled with these leaks causes a gradual return to that average resting state of around negative 65 millivolts that is a full action potential that we just went through from rest to threshold to Peak to after potential back to rest let's go through and break down a couple more components that are important here As you move from rest to threshold as the neuron reaches its peak it's raising up up up up up all the voltage-gated sodium channels are opening up you are approaching a portion of the action potential which is called the refractory period specifically within this portion of red here during the peak you are in What's called the absolute refractory period absolute refractory that means that no matter what you do no matter how much current you apply to this neuron you cannot cause another action potential to occur during this time window the neuron's voltage is already in the positive up here all of the voltage-gated sodium channels are open therefore there's nothing you can do to make it go more positive at this point so you can't cause another action potential yet what needs to occur is for the voltage to drop down more drop down more when you get into the Blue Area here say we're around here and maybe we've dropped back below now we've dropped back below zero once you drop back below zero to say negative five millivolts negative 10 millivolts you're still in the refractory period but at this point theoretically you could cause another action potential if you try hard enough if you apply enough current this is called the relative refractory period and it's a period in which most of the voltage-gated sodium channels have closed back up some are still open but most have closed and if you apply some current you can cause them to open back up and uh as potassium is rushing out at the same time potassium has been rushing out of the cell you can then cause more sodium to enter back in and cause another action potential so that's the relative refractory period And it exists from the point at which you drop below zero millivolts all the way through here even into the after potential where you're down to like neg 80 or so and then once you move out of that back to your average rest of neg 60 neg 65 we're no longer in refractory period which means that a normal average amount of stimulation epsps can cause an action potential again you don't need extra epsps as you would in the relative refractory period okay so let's review a couple of things here voltage-gated potassium channels are extremely important for the ability of the neuron to return to its resting state why does this matter the neuron cannot constantly be in a state of action it needs time to recover from that action and when it's recovering it's doing things like recycling neurotransmitter making new neurotransmitter um rest and and and and taking care of waste products all these things if you don't let the neuron go back to rest it will die that's called excitotoxicity if you excite it too much cause too many Action potentials In Too Short a period of time it will die so voltage-gated potassium channels are extremely important for the neurons ability to return to rest they click open remember when the neuron is at its peak let's say like plus 40 millivolts they all pop open potassium rushes out of the cell and that's when you get that dip down back towards the negative potassium channels also have special Gates on them and in the case of the potassium Channel what it has is what's called an n gate end gate once again this is similar to what we talked about with the Sodium channels remember the sodium channels have an M gate and an H gate the M gate is what causes the channel to click open in response to positive voltage and the H gate is like the timer which is slowly closing the door back up on the potassium channels the voltage-cated potassium channels that's the end gate okay so the voltage-gay potassium Channel opens and the end gate begins to close the trail the channel slowly it's what we call a delayed rectifier delayed rectifier because it's delayed it doesn't close it right back up it closes it slowly after it's already been opened so uh as potassium conductance decreases following the the peak of the action potential because potassium flows out so potassium conductance gets really high for a moment meaning that it can flow out of the membrane at a high rate and then what will happen is these delayed rectifiers kick in they close the voltage-gated potassium channels and now potassium conductance drops very little potassium can can flow okay this rectifies or resets the membrane potential and then it'll be the actions of the leak potassium channels and the sodium potassium pump that will gradually slow it slowly bring it back to that average neg 65. let's break down the refractory period again let's review the refractory period is a period in time in which only certain stimuli can produce an action potential and it's broken up into two parts you have an absolute refractory period And this is a time when no matter what you do you cannot cause another action potential it's a short window and it occurs when the neuron is within its its voltage is positive it's above zero if you are above zero you are in the absolute refractory phase once you drop below zero however you are in the relatively refractory phase and this is below zero before you get back below neg 60 or so below before you get back below threshold let's say so it's between let's say zero and maybe negative 40 negative 50 millivolts that would be relative refractory so this is a point where your voltage-gated sodium channels have started to close your voltage-gated potassium channels are closing back up but if you apply some stimulus you could cause those closed voltage-gated sodium channels to open back up potentially and this could cause some changes let's look at what this looks like here in another image breaking down some of these constituent Parts I'm going to give you different names for the phases of the action potential now I've been breaking it down in more simple terms now I'm going to give you the technical terms for these phases we're at rest neg65 we're going to follow this through piece by piece we're going to think about what the channels are doing at rest we're going to have closed sodium and closed potassium channels voltage-gated right closed voltage-gated sodium and potassium channels we're going to move away from rest into near the threshold and let's say the threshold here for this neuron snake 50 we cross the threshold now we're moving upward and as we're moving upward voltage-gated sodium channels are clicking open in a chain reaction this is called the rising phase the rising phase as we move from the rising phase to the peak of the action potential the peak of the action potential in which the neuron is now positively charged it's above zero this is referred to as the overshoot the overshoot in the overshoot period the neuron is said to be in What's called the absolute refractory period you cannot fire another action potential until it leaves the overshoot and enters into aspects of the falling phase now some of you who've been really observant May notice there are some differences in this graph compared to the last graph that I used for our purposes consider the absolute refractory period to be a point at which the neuron is above zero it's above zero millivolts and consider the relative refractory period to be a point where the neuron is below zero millivolts and above say negative 50 millivolts this is the falling phase at this point during the overshoot the voltage-gated potassium channels have clicked open and the voltage-gated sodium channels begin to inactivate slowly here they're inactivating in the falling phase so potassium has rushed out of the cell voltage-gated sodium channels are clicking closed the neuron is proceeding towards the negative Direction because a lot of positivity is leading in the form of potassium leaving the cell eventually we get to What's called the undershoot the undershoot this is where the neuron has dipped below the average resting potential down around neg 80 or so at this point your voltage-gated sodium channels have fully begun to reset as have your voltage-gated potassium channels and the only thing that's remaining open is your leak potassium channels and the actions of the sodium potassium pump sodium potassium pump remember is kicking three sodium ions out for every two potassium ions it brings in at this point we gradually restore the membrane potential to rest okay now you may have been wondering at this point we've seen what an action potential is but what is it that causes the action potential right you saw all this stuff about voltage-gated sodium channels and they kind of Click open automatically they click open automatically when the voltage Rises say above 50 or negative 50 millivolts maybe above negative 40 millivolts okay they begin to click open but how is it that the voltage Rises to meet the threshold in the first place right if voltage-gated sodium channels are closed how do you get this to happen well what happens is that other channels in the membrane are opened and this varies okay depending on the type of message being sent to the neuron okay the most common type of message that will get sent to a neuron that forms the basis of what's called an epsp an excitatory postsynaptic potential is a glutamate message glutamate it's the primary excitatory neurotransmitter in the nervous system we'll cover it in much more detail later but there are special channels that glutamate activates that allow sodium in they're not voltage-gated they're what are called ligand-gated ion channels so a neuron will receive a glutamate message it'll say hey open those uh open those channels and allow some sodium in that is what will cause the neuron to move towards threshold that's what's called an epsp an excitatory postsynaptic potential literally what an EPS epsp is is a small change in the membrane uh towards depolarization a small local depolarization of the membrane which pushes the cell closer toward threshold now in order for a neuron to fire an action potential you probably are going to need a lot of epsps a single epsp let's say a single glutamate message that opens up a few uh sodium channels ligand-gated ion channels for sodium it's not going to be enough generally to cause an action potential it might move the member let's say the membrane is sitting at neg65 okay you send a single epsp to the neuron and it causes a little blip it causes a brief depolarization of one area of the membrane so maybe it moves from neg 65 to neg 60. okay but what's happening now if you don't send more epsps what's going to happen remember the sodium potassium pump it's constantly kicking out three sodium ions for every two potassiums that it brings in if you don't send another epsp the sodium that you brought in is just going to get kicked back out by the sodium potassium pump and you're just going to get brought back down to next 65 okay but if you send many different epsps in a short period of time or to many different areas of the membrane to open lots of these ligand-gated ion channels for sodium now it's more likely that you're going to keep raising the membrane until it hits threshold and crosses and you have an action potential okay so what I've just been talking about uh is epsps and there's many different facets that govern epsps and whether or not an epsp is going to be likely to cause an action potential one of these is called synaptic delay synaptic delay that's the delay between an action potential and its ability to flow down a neuron and cause the release of neurotransmitter so let's say you've got Neuron a and neuron B okay Neuron a is going to send an excitatory message to neuron B but Neuron a can only send so many excitatory messages in a short window of time because in order to send an excitatory message it also has to be excited in Fire and action potential so it needs another neuron to excite it right and it can only have so many Action potentials in a short Spirit period of time the delay between the time it takes for Neuron a to fire its full action potential and ultimately to send a signal to neuron B is called synaptic delay that's one facet that influences how many epsps can be sent so hold that in your mind we're going to come back to that as we talk about two other factors that underlie postsynaptic potentials and integrating them uh to ultimately lead to or not lead to an action potential the second type of postsynaptic potential that's relevant to our discussion here is what's called an ipsp an ipsp or inhibitory postsynaptic potential an inhibitory postsynaptic potential is the opposite of an epsp it is a small hyperpolarization of the membrane that moves the cell further away from threshold so an epsp pushes the cell closer to threshold and ipsp pushes it further away from threshold here's a new term for us hyperpolarization depolarization if depolarization moves the membrane in the positive voltage Direction hyperpolarization moves the neuron in the negative direction away from threshold uh ipsps uh if epsps are usually due to the influx of sodium say from a ligand-gated ION channel maybe from a glutamate message don't worry we'll break that down later uh ipsps on the other hand are usually due to an influx of chloride ions entering the cell remember chloride is negatively charged it exists out the side the cell in in pretty good quantities and if you open an ion channel that is selective to allow sodium in it's going to flow into the cell so it's going to make it more negative so an ipsp is a type of message you can send usually being sent by Gaba which will quiet the neuron down it'll hyperpolarize it it'll make it less likely that it's going to fire less likely we'll come back to um epsps and ipsps in a little bit if not today we'll talk about it in the next action potential lecture but before we get into that the next really important thing to consider is how it is that action potentials actually flow from the Soma of the neuron down its wire its axon down to the terminal end and lead to the release of neurotransmitter how does that occur well it occurs in the nervous system through a special process in most neurons that's called saltatory conduction saltatory conduction saltatory conduction is a product of the myelin sheath and essentially the myelin sheath if you pick up a wire I don't know let's say you're sitting at your computer you pick up your mouse there's a wire coming off of it or your headphones they've got a wire coming off of them maybe uh that wire is wrapped in a rubber insulator okay and that insulator insulates the inside of the wire where the charge the electricity is Flowing it keeps it in there it's actually a form of resistance it keeps it inside you can think about myelin as like the rubber sheath covering an electrical wire in your house however there's one critical difference with myelin sheathing and everybody take a moment here to quiz yourself pause the lecture and quiz yourself what is it that wraps the myelin sheath around neurons what type of glial cell does this the answer in the central nervous system is oligodendrocytes and in the peripheral nervous system it's Schwann cells take a moment to try and remember what the difference between oligodendrocytes and Schwann cells is there's a pretty big difference the difference between oligodendrocytes and Schwann cells is that oligodendra or Schwann cells which exist only in the periphery have the capability of regenerating damaged axons oligodendrocytes which exist only in the central nervous system do not have this capability however both of them myelinate neurons they wrap them in this fatty sheath okay now here's the crucial difference between the wrapping of the wires of neurons the axons and the wires that you have sitting around your house in your cords in the nervous system the wrapping is not contiguous what I mean is that it's not a single piece instead it's more like beads on a string you get a little bit of wrapping and then a tiny little space where there's no wrapping then some more wrapping and then a little space where there's no wrapping and then more wrapping and this continues on down the length of the wire of the Axon these spaces between the layers of myelin where there is no myelin are what are referred to as nodes of ranvier nodes of ranvier and Within These spaces where there's no myelin there are concentrations of voltage-gated sodium channels and so what happens is that as electricity imagine in your mind uh an epsp epsps are being sent to this neuron they're getting sent to its dendrites okay and you send a bunch of epsps the neuron crosses threshold and it's going to fire an action potential so now imagine just imagine your mind there's like a lightning bolt here okay of electricity and it's flowing around the membrane on down to the Axon and it's going to keep moving it's going to flow down the axon until it gets to the terminal end where it's eventually going to cause the release of neurotransmitter saltatory conduction is a special type of flow of that electricity once the electricity moves from the membrane down to the axon it jumps it jumps across the segments of myelin like playing hopscotch jump jump jump jump it jumps through the nodes of romvier the areas that are unmyelinated it can't uh this is where I should say this is where again there are these high concentrations of voltage-gated sodium channels so what's literally Happening Here is that the electricity is jumping across uh shooting through it's really I'm making it look like it's jumping and you'll see that in images but in reality it's more like it's shooting through almost like a tube of toothpaste if you consider the myelin is is in like holding a tube of toothpaste in your hand and squeezing it and it causes the toothpaste to shoot out really rapidly it's kind of like that it's shooting through there and then it shoots through to this node and what happens is it gets to the node the electricity is there well that raises the membrane potential at that node of wrong VA that causes the opening of voltage-gated sodium channels sodium Flows In It regenerates the action potential and then it shoots through and goes to the next one regenerates shoots through regenerates shoots through and this is what's called saltatory conduction saltatory conduction is a really important process in the nervous system and it actually separates us from other types of animals non-mammalian species which have different types of nervous systems that are largely unmyelinated saltatory conduction allows us to send messages which are very fast along long long great distances humans have a nervous system in which we have these long arms legs and we've got a brain where everything is centralized it's called a centralized nervous system um and signals have to get set from the brain to eventually cause something like the toe on your foot to move that's a long distance of signal to travel okay well saltatory conduction because the action potential is being regenerated at each little Hopscotch node that it goes through the Integrity of the signal is maintained at a high quality because it's regenerated over and over and over again if you didn't have myelin and you just sent electricity down this this line if you didn't have myelin causing resistance on the line what would happen is that the signal would degenerate over time it would you would lose the Integrity it would go from 100 signal to like 50 signal and it would get and it would weaken over time so one of the ways that we've evolved to send messages over long distances throughout the body is saltatory conduction regenerating of the signal through these nodes of Ron VA fast jumping of the signal and it preserves signal Integrity we'll see that in other species they have a different strategy for how to do this but it tends to not be as efficient as it is in humans so humans we have very thin axons mammals in general I should say all mammals have very thin axons thin wires which are heavily insulated by myelin which means they've got a lot of resistance on them and they have saltatory conduction which causes Action potentials to regenerate and maintain their signal Integrity it allows them to travel along long distances well we'll keep that in your mind in a little bit I'm going to talk about the contrast to that let's take a look at saltatory conduction a little bit further this is talking about what I've already mentioned that regeneration okay uh each segment of node of romvier which is filled with this concentration of voltage-gated sodium channels the membrane is depolarized in that area and so it's like the electricity is moving along and you can see that here in this image what we have is a neuron and you've got four different electrodes three recording electrodes and one stimulating electrode the yellow is used to inject current into the neuron right here at the axon hillock remember the axon helic is where the Soma of the neuron begins to form into the axon of the neuron so you inject a bunch of current right here it produces depolarization and an action potential and that current begins to flow via saltatory conduction it propagates down the line until we measure it at our first electrode here it is it's measured here's the blip and then it moves down the line and we see another blip at the purple electrode and then we see another blip at the green electrode the teal electrode so you see in time the action potential is moving down the line it's being regenerated a lot across those nodes of raw VA all right let's talk about other species and how they do this they say mammals it's all centralized nervous systems heavily myelinated thin axons that use saltatory conduction but there is another type of nervous system that exists in insects in certain um other types of animals squid uh octopi jellyfish and in fact this type of nervous system is a much older more primitive type of nervous system uh the jellyfish actually uh if I'm not mistaken is the oldest most primitive form of nervous system that exists on the planet Earth today um squids have a much more complicated setup but they still follow similar principles they all have what's called a distributed nervous system so we have a centralized nervous system where we've got a brain that's the central computer and it sends signals across long distances okay squid jellyfish insects whatever they have a distributed nervous system where they have instead of a brain they have little clusters of what are called neuro pills it's like they have lots of brains but they're small brains little brains which are distributed throughout the nervous system throughout the body they're like little hubs for signal so instead of sending a signal from a really long distance from the brain to say the foot they send signals from short distances uh from Little hubs throughout the brain throughout the nervous system rather they don't have a single brain okay um and the axons the wires along which they send these signals are unmyelinated they're unmyelinated well if they're unmyelinated that means the signal is going to travel slower there's less resistance along the line which means you've got to deal with signal Integrity issues the further you send that signal the more it's going to degrade well there's a strategy to deal with that the strategy that these animals have evolved is to instead of increase uh increasing resistance along the line via myelination what they've done instead is to increase the diameter of the line they've made their axons bigger now think about axons for a moment like a pipe if you've got a really small pipe with a thin diameter you can only send so much water down at it once right you can only send so much water down at once if you've got a really large pipe you increase the diameter you can send more water this is similar to how these animals have evolved to not you they don't use saltatory conduction they don't use myelination what they do is they shoot a lot of current down a large line and they hope that most of it makes it to the end so their axons tend to be shorter but they're larger in diameter this is what's called the squid giant axon this was one of the first ways that Neuroscience experiments were done in which to understand the physiology of these things squid giant axons are so large you can see them with the naked eye so the other thing that these um uh axons do because they're not myelinated they don't have nodes of rhombier okay we said that nodes of ranvier are areas that are unmyelinated and there's a cluster of voltage-gated sodium channels as electricity flows it shoots through and jumps along between node to node to node and at each node it's regenerated well they don't have that luxury and instead they just have to run voltage-gated sodium channels along the entire length of the axon so from an energy perspective this is much less efficient than what we have but it can work so if you shoot a bunch of current down the line and you cause channels to open open open open all the way down it will flow and it will make its way down the line and you'll be able to preserve some signal Integrity but it requires more energy it requires more current it requires more channels it requires more changes in channels and it also flows slower so the signals they send are slower but they tend to send them over shorter distances and they tend to send more conduction over a large larger diameter so something like a squid or an octopus believe it or not they're relatively rather intelligent animals we're learning every day that squid are way more intelligent than we thought they're very strange creatures frankly and I would I would wager that squid octopi have the most advanced version of a distributed nervous system that exists on the planet Earth it doesn't get any better than that and yet you see they've kind of reached a potentiality cap they can move very fast when they want to and they're pretty intelligent they can learn to escape from their environment they can learn reward learning associations all sorts of stuff uh that mammals can do too right uh but there are limitations to their nervous system yet it is very Advanced now compare that to a much more uh primordial Elder and less evolved form of a distributed nervous system to the jellyfish there are a few people which would say that a jellyfish is smart a jellyfish really doesn't do much of anything it doesn't even move of its own volition really it floats it just it allows it moves with the current okay it doesn't even really move itself and it's tendrils it they don't really move much either they float along in the current and they kind of snag things that move in the current little uh Plankton whatever that move in the current and they snag it and that's how the jellyfish feeds there is very very little activity in a jellyfish nervous system it's extremely primitive in that respect and so it's interesting to think about the continuity in terms of evolution from two different types of distributed nervous system two extremes from the jellyfish to the squid the squid has certainly evolved much more mechanisms to overcome the limitations of its non-myelinated system and yet it probably will never reach the capacity or the potentiality of a mammalian centralized nervous system which is myelinated and has a saltatory conduction let's take a look at what this looks like here again in contrast here is our centralized nervous system with myelinated axons rapid 150 millisecond uh or 150 meters per second um uh in which that can move current can flow super fast and we compare that to uh the around 10 meters per second in the squid okay and we see here current flowing opens up at the node of romvier shoots down through like a tube of toothpaste down to the next layer opens up regenerates the acts of potential shoots down opens up new action potential regenerates signal Integrity preserved very fast movement all right uh summary of what we learned today so uh We've compared and contrasted the basic components of the action potential with the resting potential um and we now know how it is that the neuron moves out of the resting potential into an action potential and this is due primarily to changes in voltage-gated sodium channels but we also learned about how the neuron recovers and goes back to its resting state part of that has to do with voltage-gated potassium channels and then ultimately the closing of sodium channels and the actions of the sodium potassium pump and the actions of the leak potassium channels for the exam you should be able to go through and look at on that figure there's two figures in here of the action potential and you should be able to do two things number one if you are given a portion of the action potential if I say overshoot to you which is the peak of the action potential you should be able to tell me what the channels are doing at that point what's happening in the overshoot well if you're at the peak of the action potential all of the voltage-gated sodium channels are open and now the voltage-gated potassium channels are going to click open and potassium is going to rush out that's how you should be able to break this down in your head number two make sure you can identify the different phases okay rest threshold Rising overshoot falling undershoot return to rest and what's going on with those channels take some time to think about this there is a great summary video on canvas um below this lecture which will take you through the exact process I just described in the video it's a few minutes long and you'll see these channels opening and closing in time throughout the action potential we'll pick back up in the next lecture with action potential part two and we'll see how other factors synaptic factors can influence these processes