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Physiology Question: Membrane Potential

Discussion in 'MCAT Study Question Q&A' started by CanadianBebe, Dec 3, 2008.

  1. CanadianBebe

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    I'm a bit confused about something. When considering the effects of increasing external potassium concentration, this results in depolarization of the membrane. Then 'apparently', sodium channels availability decrease (which causes an increase in threshold??) and there is an increase in potassium channel availability (which decreases action potential).

    Why exactly? I thought depolarization was what opened the voltage-gated sodium channels ...

    Thanks!
     
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  3. TheBoondocks

    TheBoondocks StreetFighter 4 Virtuoso
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    I'll give it my best shot. The membrane potential is largely determined by K+ because it is more permeable than Na+. There is more K+ intracellulary. If you increase the external concentration, you're depolarizing/ reducing the membrane potential according to the boltzman equation (nernst equation with all ions involved). This is because the potential is a measure of the force required to stop flow. For the case that K+ is 10 times greater inside than outside, the potential needed to stop flow is -60mv. This varies. By adding charge outside, there is less tendency for K+ to flow, the concentration difference becomes less and this is why the membrane decreases. Let's say now it's only 5 times greater, then the membrnae potential would drop to -30. That's the short explanation of the membrane depolarization. As a result of this, the membrane is closer to threshold and Na+ channels can now flow since the membrane has been depolarized. into the cell. K+ channels flow out at their regular voltage to lower the AP. The reason threshold increases is since the membrane is constantly depolarized, Sodium channels aren't removed from the cell, so the eventual result is a Na+ reduction. I'd consult a physiology text, I'm in class right now and will update my response. Too much K+ occures in diseases like hypercholestemia. The extra K+ causes membrane to be close to threshold and then causes sustained contractions.

    You're correct. Na+ channels are released as a result of depolarization. However, how that depolarization comes about is irrelevent. Normally an AP comes and depolarizes the membrane, and then Na+ is released. The memrane potential can also be depolarized or hyperpolarized by altering the concentrations of the surrounding ions. This is how neurobiologists and physiologists conduct research. Normally the AP is short and membrane is depolarized for a short period. However, here, it is depolarized for as long as there is a large extracellular concentration.
     
  4. Airplay355

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    My best guess...

    Resting membrane potential is determined by the Na+/K+/ATPase pump. Both Na and K are positive ions so it does seem a little strange that adding a positive ion to the cell makes it negative. The reason this happens is because of the ATPase pump I mentioned. Don't forget that when I say the cell is negative, I mean the inside of the membrane is negative relative to the outside.

    Resting membrane potential is kept around -90mv because this is close to the equilibrium potential of K+. Passive K+ channels (K1 channels) are open while the cell is at rest, allowing K+ to passively diffuse out of the cell. Sodium diffuses into the cell, but is removed by the ATPase pump. Even though K+ is brought into the cell by the ATPase pump it can passively diffuse back out.

    There are other things that contribute to the resting membrane potential. Large organic ions (like proteins) are present in higher concentrations in intracellular fluid compared with extracellular fluid.

    Hyperkalemia can cause a buildup of K+ inside as a result of a decreased concentration gradient caused by more extracellular calcium. K+ won't passively diffuse through k1 channels as readily leading to a build up of the positive ion. This slightly depolarizes the cell and may lead to some voltage gated sodium channels opening. Since these channels just opened they will eventually be in a refractory period which leaves them incapable of opening again. If the cell is stimulated to depolarize while some of the sodium channels are in refractory it will be harder for the cell to reach threshold because it will take longer for intracellular Na+ concentrations to reach appropriate levels. Taking longer to reach threshold and thus completely depolarize means a slower velocity action potential.

    This doesn't always apply to cardiomyocytes, as hypokalemia can actually make them hyperexcitable leading to arrhythmias. That could have to do with altering different K+ currents though...not important to the question just an FYI.
     
    #3 Airplay355, Dec 9, 2008
    Last edited: Dec 9, 2008
  5. TheBoondocks

    TheBoondocks StreetFighter 4 Virtuoso
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    That's not true. Only 8-9 mv of the resting membrane potential is maintained by the pump. Most of it is due to greater conductance of the K+ ions. Since K+ has greater conductivity, the membrane potential is closer to K+ around -85mv than Na (+58mv). During an AP, conduction for Na+ increases and they rush in. However, without the Pump, the concentration difference of K+ and Na+ wouldn't be maintained. The pump is crucial for maintaining the membrane potential, but contributes little to the actual potential value. Maybe it's semantics, but too many people think it's the pump that determines the membrane potential. It's job is to maintain the concentration difference so that Na can rush in when it is depolarized. The only ion which is at equilibrium is Cl-. That's why K+ leaks out of the cell and must be contintually pumped back in by the pump. The key is conductance. Finally, Hyperkalemia is excess K+ outside the cell, not inside. It is excess K+ in the interstitial fluid which is different from intracellular fluid. The membrane potential is lowered. In hyperkalemia, the membrane potential becomes more positive because there is more K+ outside the cell. Consequently, it's closer to threshold, and Calcium build up as you said leads to sustained contractions.
     
    #4 TheBoondocks, Dec 13, 2008
    Last edited: Dec 13, 2008
  6. isaacmn

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    ok, i see much emphasis on K+ here than I do Na+...depolarization is largely due to Na+. in event to depolarization, the inside of the membrane is more negative (70mv)., resting potential, because it contains a lot of negatively charged proteins. when Na+ channel is activated, it moves into the cell depolarizing that memberane., reaching what is called a threshold first around -50mv, then to +30mv or something like that. The inside of the mebrane is now positive, that is when Action potential is fired. In events to repolarization of the membrane back to its resting potential at -70mv, Na+ moves out of the cell and the channel is deactivated, which automatically activates the K+ channel, the K+ which is inside of the cell now moves out of the cell to get the cell back to its resting potential. All these processes are all actively done. so I guess, in summary during Action potential, inside of the cell is more + than the outside and during resting potential, the inside is more negative than the outside. Na+ is the biggi in depolarization and K+ for repolarization.
     
  7. Airplay355

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    The resting membrane potential is close to the equilibrium potential of K+ because K+ is actively placed inside the cell by the ATPase pumps. If there were no ATPase pumps, cells would become more positive and closer to Na+'s equilibrium potential. So, yes, Na+/K+/ATPase pumps are responsible for creating the K+ concentrations that lead to diffusion of K+ in such a way that the resting membrane potential is negative as well as creating a Na+ gradient that allows for quick diffusion into the cell when appropriate ion channels are opened.

    K+ rushes out of the cell at rest because K+ channels are open at rest while sodium channels are closed. Not because K+ is just better at diffusing. These are passive channels, not active pumps.

    I know hyperkalemia is excess K+ in extracellular fluid. However, if there's a higher concentration of K+ outside the cell, there will be less diffusion of K+ from the INSIDE of the cell to the OUTSIDE of the cell. Less diffusion outwards means more K+ inside the cell then normal because it is not diffusing outwardly as fast.

    What you're saying doesn't really make sense. You said hyperkalemia lowers membrane potential (I guess that means more negative) and then right after you say it makes the membrane potential more positive. Which one is it?

    Also, can you explain the mechanism behind hyperkalemia making a cell more positive if what I described is wrong?
     
  8. TheBoondocks

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    The pump is necessary. I don't disagree with you there. However, it's contribution to the membrane potential is small. The primary cause of the membrane potential is permeability to K+. Since there are K+ leak channels, K+ efflux occurs. The concentration difference allows K+ to leave the cell but its electrical gradient is in the opposite (inward) direction. I look at the general effect. You're right, K+ isn't more permeable than Na+. However, with the help of the leak channels the net effect is that they are. The reason the membrane is closer to K+ is because of the leak channels of K+ which increase the permeability of K+. Na influx is insignificant. However, like you said, without the pump bringing K+ back in, then the concentration difference is lost and the membrane potential becomes more positive. The pump is electrogenic and contributes 8-9 mvs and maintains the concentration. In Neurobiology, my professor harped on this fact. The pump is necessary but it is permability that determines membrane potential. This is why during an AP, it becomes more positive because now Na+ is more permeable.


    I was only clarifying what you said, not trying to disprove it. I just wanted to make sure you understood the difference, I didn't until my Neuro class this semester. Also, realize that it's only a small amount of molecules that cause this potential. The overal charge is zero, but due to unequal spacing at the edge of the membrane, it's enough to create the -70 mV you stated.

    Hyperkalemia makes the membrane more positive. There is an increase in plasma K+. Increases in extraceullar K+ makes the MP more positive. I said lowered as in less negative, that is my bad. The refractory period and Na+ stuff you stated is dead on. Again, wasn't disproving anything you said, just clarifiying for anyone reading. Without the pump, no membrane, but the pump itself contributes little to the membrane. :thumbup:
     
  9. Airplay355

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    Gotcha. I guess I freaked out a little more then I should have because I had a CV phys final coming up and I started questioning everything I knew about membrane potential. Sorry bout that.

    I had never heard that the pump only contributes 8-9 mV of potential. Most of the emphasis gets put on the pump in the class I took, because when it fails during periods of ischemia, you can end up developing re-entrant loops. I suppose that's more clinically relevant.

    Thanks for clarifying.
    :D
     
  10. 229141

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    Depolarization occurs as Na+ activation gates open and Na+ rushes in and Na+ deactivation gates close..
     
  11. TheBoondocks

    TheBoondocks StreetFighter 4 Virtuoso
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    That's how the main depolarization occurs. However, first, it must reach threshold. It can reach threshold through a variety of ways. One is to alter K+ which depolarizes to threshold to allow for Na+. She was confused by this. Na+ don't open by themselves. There must be an initial depolarization to cause their release which in turn causes the membrane to move towards +58 mv but doesn't actually reach it because they close as you said and K+ leaks out.
     

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