Refractory Periods | Action potentials in neurons

In this video, I'll quickly summarize the

action

potential in

neurons

and show you where the absolute and relative

refractory

periods

begin and end. Refractory

periods

are those in which

action

potentials

are impossible or harder than normal. Then, at the end of the video, I'll give you a cool (and super important) reason why you should care A LOT about

refractory

periods. Are you ready? :) Let's do it! Welcome to “Physio Flip”! An inactive neuron typically starts with a resting membrane potential of around -70 millivolts. At this membrane potential, all voltage-gated sodium and potassium channels are closed. To help us keep track of these channels more easily, I'm going to put a little key here in the corner.

Remember that the channel with an activation gate AND an inactivation gate is the voltage-gated sodium channel. This one drawn with a single gate is the voltage-gated potassium channel. When the neuron is at rest (with the gating gate closed), I like to think of the voltage-gated sodium channel as a closed gate. While it is closed, we can open it if we pull hard enough. The way to "open" this sodium channel, open the gating gate, and initiate an action potential is to make the inside of the cell positive enough to about -55 millivolts. If we reach this threshold value, we can see that the sodium activation gate opens, allowing sodium to enter the cell, depolarizing the membrane and making it more positive.

At this point, I like to think of sodium channels as a door that has been completely opened. But since these channels are as open as possible, we cannot open them AGAIN during this stage; They are currently fully occupied. Think about it. If you just opened this door here and then someone asked you to open it AGAIN, you'd probably say, "Uhhhh I can't, it's already open..." The same thing happens here: if the voltage-gated sodium channels are already open, but we would like to open them again to initiate another action potential, the neuron would say: "Uhhhh, I can't, they are already open and fully occupied." So, I'm going to color these voltage-gated sodium channels and this depolarization phase red to help us remember that the sodium channels are occupied and cannot be used to initiate another action potential during this phase of the current action potential.

By the way, remember that voltage-gated potassium channels are still closed during this phase. However, we will eventually have to end the action potential in order for this neuron to rest again. That's the job of the inactivation gate: it will close, blocking the sodium channel and preventing more sodium from entering. Remember that what also happens is that the voltage-gated potassium channels open, allowing potassium to flow out, repolarizing the cell making it more negative again. The voltage-gated sodium channel is now inactive since that little ball and chain (the inactivation gate) is blocking the channel. In this inactive state, I like to think of the sodium channel as a closed door.

Not only is it closed, but the inactivation door will block the channel and prevent it from opening no matter what. So, I'm also going to color these sodium channels red in this phase of the action potential, which will help us remember that these voltage-gated sodium channels are "locked", turned off, and cannot be used to initiate another action potential. during this action potential. Repolarization phase. And in fact, this entire region that I highlighted in red, from -55 to around -70, is known as the "absolute refractory period." The word "refractory" sounds like a fancy word, but I like to think of it as another way of saying the word "resistant." So if a part of the neuron is in the absolute REFRACTORY period, this part of the neuron is absolutely RESISTANT to initiate another action potential no matter what.

We saw that during depolarization, when sodium CHANNELS are fully open, we cannot initiate another AP because all sodium channels are already open and fully occupied. Then, when the cell repolarizes and becomes more negative, we saw that the inactivation gate blocks or inactivates this channel. In this state, the channel is “blocked” and cannot be opened by any stimulus, no matter how strong. By the way, if you're curious why the inactivation door can't be opened, check out the comments below :). We'll have to wait a little longer before we can start the next one. However, around -70 mV, the sodium channel "lock" is unblocked and the channel returns to its original shape.

You can see that this sodium channel looks the same as it did at the beginning. As a result, starting here around -70 mmV, we can now start another action potential again (although the current one has not finished yet). So the absolute refractory period is over! Hurrah! BUT, while we can start another AP, it will be more difficult than normal. :/ This is because the voltage-gated potassium channels remained open, allowing potassium to continue leaving the cell, causing the cell to become hyperpolarized (even more negative than the resting state). However, eventually, all voltage-regulated channels close and restore to their original form. as a result of this hyperpolarized and negative state.

Throughout this region that I highlighted in white (the hyperpolarized region), it is POSSIBLE to start another AP but it will be more difficult than normal. This is why. If we are at -90 millivolts, it will be much more difficult to reach the -55 threshold than if we started from here at -70. The potassium coming out and hyperpolarizing the cell has made it much harder and will require a much stronger stimulus for another AP to begin. That is why this region (from about -70 to about -70) is called the "relative refractory period." The membrane is relatively (but NOT absolutely or COMPLETELY) resistant to initiating another action potential.

When we finally return to the normal resting membrane potential of -70, we end the relative refractory period and a normal regular stimulus can bring us to the threshold of -55 once again. Alright, I know what you're thinking: WHO CARES????!!!! WHY ARE WE TALKING ABOUT THESE REFRACTORY PERIODS? WHY DO I NEED TO KNOW THIS?! THIS. IS. SO. IDIOT. I hear you'. Sorry :D But let me give you one good reason why you should care a lot about these refractory periods and why they are so interesting and important. If you've ever been to the dentist, you know that it can be painful at times.

They have needles, beaks, hooks and they like to use them. For this guy at the table, things could get ugly and painful. For procedures that may cause pain, dentists often use this medication called lidocaine. It works by preventing cells from firing action

potentials

, making cells resistant or REFRACTORY to being stimulated. See?!!! There is that word “refractory”!!! I told you it was important! Let's see how lidocaine works. Lidocaine is a drug that binds to voltage-gated sodium channels and keeps them in this inactive, blocked state where the inactivation gate is closed. However, we know that if the sodium channels look like this, another action potential is not possible (no matter what!) because these sodium channels are absolutely refractory and absolutely resistant to initiating another action potential.

Let's take a closer look at a neuron treated with lidocaine to see how it works. You can see that this neuron has all of its voltage-gated sodium channels inactive due to the presence of lidocaine. That means that even if this neuron receives a very, VERY strong stimulus (e.g. a large amount of neurotransmitter being released or the dentist cutting your gums with a knife), no matter how strong the stimulus is, these

neurons

will not activate. and they will not activate. action potentials to the brain. But if your brain never receives the signal that your mouth is being damaged, it won't feel or perceive the pain!

So, thank you to lidocaine and the absolute refractory period for helping us get through our painful dental visits!