Depolarization and repolarization.

[starbaduk]

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To me, it's intuitive to think of depolarization as membrane potential becoming more positive.

But after the action potential and hyperpolarization, positive change in membrane potential toward resting state is called repolarization? (rather than depolarization?)

That's what the answer key says, but I would like a confirmation. Thanks 🙂

 

[Will Hunting]

To me, it's intuitive to think of depolarization as membrane potential becoming more positive.

But after the action potential and hyperpolarization, positive change in membrane potential toward resting state is called repolarization? (rather than depolarization?)

That's what the answer key says, but I would like a confirmation. Thanks 🙂

Yes, and this is to avoid confusion. It's repolarizing to the normal state. It is becoming more positive but is still more negative than the resting state until it returns back to the resting membrane potential. You hit the nail on the head. That is how you should think.

with this in mind, answer this question: If the K+ concentration outside the cell is increased, what will this do the the resting membrane potential?

A. Nothing
B. make it more positive
C. make it more negative
D. 0

As a follow up, would the membrane be more amenable to depolarization?
A. Yes, because it's more negative
B. Yes, because it's more positive
C. No, because it's more negative
D. No, because it's more positive

this is how you should approach the MCAT, ask what if questions and be able to answer them.

 

[starbaduk]

Yes, and this is to avoid confusion. It's repolarizing to the normal state. It is becoming more positive but is still more negative than the resting state until it returns back to the resting membrane potential. You hit the nail on the head. That is how you should think.

with this in mind, answer this question: If the K+ concentration outside the cell is increased, what will this do the the resting membrane potential?

A. Nothing
B. make it more positive
C. make it more negative
D. 0

As a follow up, would the membrane be more amenable to depolarization?
A. Yes, because it's more negative
B. Yes, because it's more positive
C. No, because it's more negative
D. No, because it's more positive

this is how you should approach the MCAT, ask what if questions and be able to answer them.

Thanks for the clarification.

My guess is that, since K+ concentration is usually higher inside the cell than outside (due to Na/K ATPase), if K+ concentration outside the cell is increased, K+ will leak more slowly than under normal condition. My guess is that resting membrane potential will become more positive.

For the second question, assuming my answer to the first question is correct, threshold potential would be reached more readily because the membrane potential is more positive. B?

 

[Charles_Carmichael]

Increased extracellular K+ concentration whould make the resting membrane potential more positive, but it would NOT be easier to depolarize: The Na+ channel inactivation gates are more likely to be closed due to the more positive membrane potential and this will decrease the inward movement of Na+ (even though the activation gates are open). This is why hyperkalemia can cause muscle weakness (it makes it harder to fire action potentials).

 

[coffeebythelake]

Increased extracellular K+ concentration whould make the resting membrane potential more positive, but it would NOT be easier to depolarize: The Na+ channel inactivation gates are more likely to be closed due to the more positive membrane potential and this will decrease the inward movement of Na+ (even though the activation gates are open). This is why hyperkalemia can cause muscle weakness (it makes it harder to fire action potentials).

This depends on the level of extracellular K+ increase. Slight depol favors Na channel firing. Significant depol prevents it.

 

[Charles_Carmichael]

This depends on the level of extracellular K+ increase. Slight depol favors Na channel firing. Significant depol prevents it.

Yea, that's true. I should've mentioned that in my original post.

 

[Will Hunting]

Thanks for the clarification.

My guess is that, since K+ concentration is usually higher inside the cell than outside (due to Na/K ATPase), if K+ concentration outside the cell is increased, K+ will leak more slowly than under normal condition. My guess is that resting membrane potential will become more positive.

For the second question, assuming my answer to the first question is correct, threshold potential would be reached more readily because the membrane potential is more positive. B?

Correct. Kaushik is wrong. I checked my medical physiology book and yes you answered both questions correctly.

 

[Will Hunting]

Increased extracellular K+ concentration whould make the resting membrane potential more positive, but it would NOT be easier to depolarize: The Na+ channel inactivation gates are more likely to be closed due to the more positive membrane potential and this will decrease the inward movement of Na+ (even though the activation gates are open). This is why hyperkalemia can cause muscle weakness (it makes it harder to fire action potentials).

True, but you forget that it's still negative and equilibrium potential is +50mv so there is still strong movement for Na+ into the cell. So, your argument doesn't hold. Well done guys.

 

[Charles_Carmichael]

True, but you forget that it's still negative and equilibrium potential is +50mv so there is still strong movement for Na+ into the cell. So, your argument doesn't hold. Well done guys.

I'm not at home right now, so I don't have access to a textbook, but I believe what eikenhein and I said is true. I realize that the membrane potential is still negative, but the thing is, the more depolarized you are from the normal membrane potential, the higher the probability is that the slow-acting inactivation gates on Na+ channels are closed. If these gates are closed, Na+ ions cannot move into the cell; it doesn't matter if the potential is closer to 0.

So, with slight depolarization, as eikenhein mentioned, it would be easier to fire an AP (because slight depolarization is not enough to cause closure of the Na+ inactivation gates). But once you get more depolarization, the inactivation gates on some Na+ channels are more likely to be closed; this makes it harder to fire action potentials (since Na+ ions cannot move inwards).

If you had specified in your original question that the increase in extracellular K+ was only slight, then I would agree with you that I'm wrong. Hope this clears up my thought process behind answering the question the way I did. Like I mentioned, I'm not home right now and don't have access to a textbook, but this was how I understood the process when I first learned it. If anything is wrong with my explanation, feel free to point it out. 😛

Edit: I'm back home and I looked into the Costanzo physiology textbook. Here's a description regarding a case study of hyperkalemia in the section discussing action potentials:

"When the blood [K+] is elevated, the concentration gradient across the cell membrane is less than normal; resting membrane potential will therefore be less negative (i.e., depolarized). It might be expected that this depolarization would make it easier to generate action potentials in the muscle because the resting membrane potential would be closer to threshold. A more important effect of depolarization, however, is that it closes the inactivation gates on Na+ channels. When these inactivation gates are closed, no action potentials can be generated, even if the activation gates are open. Without action potentials in the muscle, there can be no contraction."

So yea, there cannot be a strong inward Na+ current if the gates are closed. Like eikenhein mentioned previously, slight depolarization would make it easier to depolarize the cell further (because it wouldn't affect the Na+ channels adversely), but if the depolarization is beyond a slight depolarization (ie. a much higher extracellular K+), further depolarization will be inhibited due to the closing of these inactivation gates; there cannot be an inward Na+ current if the gates are closed! You have to take into account the properties of the ion channels and not just the fact that the inside of the cell is still negative. Hope this helps.

 

[glia25]

The way I have always learned about inactivation versus closure of channels is with regard to the AP having occurred. Na+ channels is fast activating channels (K+ channels are kinetically slower), during depolarization both channels actually begin the process of opening; but it just takes longer for the K+ channels to complete it hence hyperpolarization past the resting membrane potential. The Na+ channels do not inactivate until the Na+ has flowed into the neuron, usually they are inactivated following the action potential's propagation.

As for the depolarization vs. repolarization vs. hyperpolarization. I always think about everything based off of membrane potential. Depolarized is more positive than the resting membrane potential >-70, hyperpolarization is <-70, and repolarization is an attempt to get back to membrane potential again (~re analogous with again). Keep in mind that a membrane potential is relative to the organism so the -70mV differs depending on what cell you are dealing with.

The concentration of the ions and the permeability of a membrane to the ion will determine the potential. Think the Goldman-Hodgkin-Katz equation which takes all of these factors into account. A depolarized membrane is more likely to fire an action potential because the membrane is now closer to its threshold and more Na+ channels are likely to be open and external potassium ALMOST ALWAYS implies a hyperpolarization as many cells naturally have more internal potassium. The cell is responding in some way such that it will be less likely to trigger an AP.

Does this settle anything?

 

[glia25]

...and I think that the idea of an equilibrium potential is well beyond the MCAT, unless you are forced to do an application following explanation of what one is...

 

[Charles_Carmichael]

The way I have always learned about inactivation versus closure of channels is with regard to the AP having occurred. Na+ channels is fast activating channels (K+ channels are kinetically slower), during depolarization both channels actually begin the process of opening; but it just takes longer for the K+ channels to complete it hence hyperpolarization past the resting membrane potential. The Na+ channels do not inactivate until the Na+ has flowed into the neuron, usually they are inactivated following the action potential's propagation.

As for the depolarization vs. repolarization vs. hyperpolarization. I always think about everything based off of membrane potential. Depolarized is more positive than the resting membrane potential >-70, hyperpolarization is <-70, and repolarization is an attempt to get back to membrane potential again (~re analogous with again). Keep in mind that a membrane potential is relative to the organism so the -70mV differs depending on what cell you are dealing with.

The concentration of the ions and the permeability of a membrane to the ion will determine the potential. Think the Goldman-Hodgkin-Katz equation which takes all of these factors into account. A depolarized membrane is more likely to fire an action potential because the membrane is now closer to its threshold and more Na+ channels are likely to be open and external potassium ALMOST ALWAYS implies a hyperpolarization as many cells naturally have more internal potassium. The cell is responding in some way such that it will be less likely to trigger an AP.

Does this settle anything?

Regarding the bolded part, depolarization activates both the activation gate and the inactivation gate; the inactivation gate closes slower than the activation gate opens. So Na+ ions come inwards a moment before the inactivation gate closes. But significant depolarization closes the inactivation gates and they do not reopen until the membrane is repolarized close to its membrane potential.

So the problem is, while you're right that Na+ ions come in before the inactivation gates close, if the membrane potential is made more positive due to hyperkalemia, the inactivation gates will be always closed because repolarization towards the normal membrane potential is needed for them to open up again. And if the inactivation gates are closed, the cell is in a perpetual refractory period; it's conductance to Na+ is 0.

And you're probably right about not needing this much detail for the MCAT! 🙂

Edit: Maybe it's clearer to say that as the membrane potential gets more depolarized, the probablity of the activation gates on Na+ channels being open increases, while at the same time, the probability of the inactivation gates closing also increases. And if the inactivation gates are closed (due to hyperkalemia and no repolarization to the "normal" resting membrane potential), there's no inward Na+ current. So, there's no depolarization or action potential firing. It's the same as the cell being in a refractory period. It would be harder to depolarize it. Hope this helps.

Edit 2: Read what I quoted from the Costanzo physiology textbook (which a lot of medical students swear by) in my previous post. It basically says what I've been saying till now.

 

[Chowdder]

That's a lot of writing even for a guy studying neuroscience 😛. Anyways my take on this is that as long as the depolarization due to extracellular K+ maintains the resting membrane potential below the threshold of VG Na+ channel activation, then it should increase excitability. Think someone have mentioned this already. 👍

 

[Charles_Carmichael]

That's a lot of writing even for a guy studying neuroscience 😛. Anyways my take on this is that as long as the depolarization due to extracellular K+ maintains the resting membrane potential below the threshold of VG Na+ channel activation, then it should increase excitability. Think someone have mentioned this already. 👍

Yes, this is basically what I've been saying. Hopefully, my explanations weren't confusing! 😛

 

[Will Hunting]

Yes, this is basically what I've been saying. Hopefully, my explanations weren't confusing! 😛

Oh, then we agree. I assumed this to be the case. If you meant that it went from say -70 to -50. However, I think depolarization is at about -40, and if the resting goes to -30, then yes, it would be less excitable. Well done guys. I also benefited from this.

 

[Charles_Carmichael]

Oh, then we agree. I assumed this to be the case. If you meant that it went from say -70 to -50. However, I think depolarization is at about -40, and if the resting goes to -30, then yes, it would be less excitable. Well done guys. I also benefited from this.

I'm glad we agree. However, the cell would be less excitable even if the resting potential goes to around -60mV. The reason is that as the potential gets more depolarized (not just depolarized enough to fire an AP), the probability of Na+ channel inactivation gates closing increases. So, the resting potential does not have to get to -40mV in order to become less excitable. At -60mV, for example, the probability of a Na+ channel being closed is around 0.1, if I remember correctly; so, you don't need to get to -40mV before becoming less excitable; it starts happening before then. Hope this helps! 🙂

 

[ThrusH]

As I'd rather not clutter up the Q&A section with more threads regarding the exact same topic, I was wondering if anyone could help me understand this explanation a little better.

It's from a TRP exam hopefully I'm not breaking any rules with this.

In the passage, it said that the resting potential of rod cells is much higher than that of normal cells due to the constant influx of sodium. My thought process on this one was: At t=1, it's already past the hump and is now becoming more positive, i.e. depolarization or repolarization. It has not crossed where the RMP would be, thus it cannot be repolarizing and is depolarizing.

However, as you can see, the answer is hyperpolarizing. What's am I missing?

 

[golgiapparatus88]

ThrusH, they want the point on the graph AT 1 second. Not leading up to the event or after the event. I see why this could be confusing put I think it's easier to take only the point that they care about (t=1) and not what is going to happen after.

 

[Charles_Carmichael]

As I'd rather not clutter up the Q&A section with more threads regarding the exact same topic, I was wondering if anyone could help me understand this explanation a little better.

It's from a TRP exam hopefully I'm not breaking any rules with this.


In the passage, it said that the resting potential of rod cells is much higher than that of normal cells due to the constant influx of sodium. My thought process on this one was: At t=1, it's already past the hump and is now becoming more positive, i.e. depolarization or repolarization. It has not crossed where the RMP would be, thus it cannot be repolarizing and is depolarizing.

However, as you can see, the answer is hyperpolarizing. What's am I missing?

At time = 0, the membrane potential is -30mV (the graph shows you that the light pulse [the stimulus] occurs after time = 0 further telling you that the RMP is -30mV) and at time = 1, the membrane potential looks to be about -90mV. This means that the membrane potential became even more negative. So, this is hyperpolarization. It's only depolarization if the membrane potential becomes more positive.

Make sure you understand the definitions of depolarization, repolarization, and hyperpolarization. That alone gives the answer away.

Hope this helps.

Edit: After rereading your question, it seems like you're more confused that the time = 1 corresponds to slightly after the minimum, where the answer could potentially be repolarization. It's a bit close to over-think it like that, IMO, but I can understand the ambiguity. Either way, though, it looks like you chose depolarization, which is wrong. It seems like a toss-up between hyperpolarization and repolarization. Since, at t = 1, it's much closer to the minimum, I would probably go with hyperpolarization...I don't think you'd see something ambiguous like this on the actual MCAT though.

 

[golgiapparatus88]

I don't think you'd see something ambiguous like this on the actual MCAT though.

Agreed. At first glance I thought hyperpolarization but the more I think about it, the more I think it could be a toss up between that and repolarization. On the real test they would probably give a larger portion of the graph.

 

[Charles_Carmichael]

Really, the way I think about it is if the membrane potential is more positive than the RMP, then it's depolarization; otherwise, it's not. At t = 1, the membrane potential is much more negative than RMP and so, it's in a hyperpolarized state. But yea, like I said, it's highly unlikely that you'll get something ambiguous on the actual MCAT.

 

[eldoctor]

As I'd rather not clutter up the Q&A section with more threads regarding the exact same topic, I was wondering if anyone could help me understand this explanation a little better.

It's from a TRP exam hopefully I'm not breaking any rules with this.

However, as you can see, the answer is hyperpolarizing. What's am I missing?

Guys, you have to realize that photoreceptors such as rods (which is what they are giving you) are HYPERPOLARIZED in response to light. This is an intrinsic property of these cells, which is probably why it's confusing, since you'd expect that they depolarize.

 

[fizzgig]

Guys, you have to realize that photoreceptors such as rods (which is what they are giving you) are HYPERPOLARIZED in response to light. This is an intrinsic property of these cells, which is probably why it's confusing, since you'd expect that they depolarize.

i agree that this is probably the point they were trying to get at. it's excitation of the cell but it's upside down because it's a rod cell.

 

[bullsfan1986]

In order to repolarize wouldn't you need to first depolarize? Because the x axis starts at t=0 I don't think there is any ambiguity between repolarization and hyperpolarization in this problem.

 

[eldoctor]

i agree that this is probably the point they were trying to get at. it's excitation of the cell but it's upside down because it's a rod cell.

Correct

 

[ThrusH]

Guys, you have to realize that photoreceptors such as rods (which is what they are giving you) are HYPERPOLARIZED in response to light. This is an intrinsic property of these cells, which is probably why it's confusing, since you'd expect that they depolarize.

i agree that this is probably the point they were trying to get at. it's excitation of the cell but it's upside down because it's a rod cell.

This is true, but the question does not ask what state the cell is in. It asked what is happening at t=1.

My thought was that since rods are have an intrinsically higher RMP of about -30mV and get hyperpolarized by light, they would either be repolarizing or depolarizing (I actually put a piece of paper up to my monitor when I was taking the test, lol). Since it looks like the graph peaks slightly before t=1 and begins returning to RMP at t=1 I went with depolarizing. I thought repolarizing only would occur if it depolarized past RMP, similar to how other cells hyperpolarize past RMP and repolarize back to RMP.

According to wiki (you can pretty much ignore everything up until the end):

Revert to the resting state
Rods make use of three inhibitory mechanisms (negative feedback mechanisms) to allow a rapid revert to the resting state after a flash of light.
Firstly, there exists a rhodopsin kinase (RK) which would phosphorylate the cytosolic tail of the activated rhodopsin on the multiple serines, partially inhibiting the activation of transducin. Also, an inhibitory protein - arrestin then binds to the phosphorylated rhodopsins to further inhibit the rhodopsin's activity.
While arrestin shuts off rhodopsin, an RGS protein (functioning as a GTPase-activating proteins(GAPs)) drives the transducin (G-protein) into an "off" state by increasing the rate of hydrolysis of the bounded GTP to GDP.
Also as the cGMP sensitive channels allow not only the influx of sodium ions, but also calcium ions, with the decrease in concentration of cGMP, cGMP sensitive channels are then closed and reducing the normal influx of calcium ions. The decrease in the concentration of calcium ions stimulates the calcium ion-sensitive proteins, which would then activate the guanylyl cyclase to replenish the cGMP, rapidly restoring its original concentration. The restoration opens the cGMP sensitive channels and causes a depolarization of the plasma membrane.[5]

I know the actual MCAT won't be as ambiguous, but I just wanted to make sure my logic was/is correct.

 

[fizzgig]

i see what you're saying thrush. i think, anyway.

you're right, these cells go through hyperpolarization then depolarization to resting state, and i'd think it would be technically incorrect at least to call that return to resting state repolarization because it is not polarizing again, but un-polarizing again.

this may be one of those crap situations where you are looking too closely at where they put a peak on a less than stellarly made graph (i feel sometimes if i can't tell by looking pretty roughly on a graph i may be missing something). their t=1 marker is roughly 'at the peak'... where the cell is still in a state of hyperpolarization, and the recovery depolarization hasn't really gotten going yet. that would be my guess as to why A is correct. you are looking superclosely and saying well technically it looks like the curve has peaked and is staarrrting to go back up ever so slightly. that might be too detailed of a view? :/

 

[Charles_Carmichael]

Think of it like this: during the time period between when the light pulse occurs and t = 3s, what state would you characterize the membrane potential as? Hyperpolarized or depolarized with respect to the RMP? That's how I thought about it to come up with hyperpolarization as the answer. I mean, even in a normal action potential, during the repolarization stage, the membrane potential is still technically in a depolarized state (compared to the RMP) until the RMP is reached.

 

[fizzgig]

good point. i was stuck in the mindset, as thrush might have been, that they were asking for 'what process is happening', like is it becoming more polarized or less. but if you look at it as just asking a question of state, then that simplifies it for sure.

 

[ThrusH]

Think of it like this: during the time period between when the light pulse occurs and t = 3s, what state would you characterize the membrane potential as? Hyperpolarized or depolarized with respect to the RMP? That's how I thought about it to come up with hyperpolarization as the answer. I mean, even in a normal action potential, during the repolarization stage, the membrane potential is still technically in a depolarized state (compared to the RMP) until the RMP is reached.

I think you figure it out... Thank you! This question has been driving me nuts! I was probably looking too much into the details. I assumed that if it was asking for the state, it would have said "Hyperpolarized" as opposed to "Hyperpolarization."

At least the actual MCAT won't be this controversial... at least I hope not!