Hyperkalemia question

[staphaureus]

Can someone please explain this. With intracellular K concentration held constant, increasing extracellular will increase (make more positive) the membrane potential, depolarizing it.

This doesn't make sense to me. Intuitively, I would expect that increasing extracellular K+ would make the intercellular even more negative with reference to the extracelluar.

I can understand that increasing extracellular K+ with freely permable K+ can increase intracellar K --> deplarization, but the question specifically said the intracellular K was held constant. Thanks

---

Members don't see this ad.

 

[Krazykritter]

Deleted for errors...Will post again later w/ better answer

 

[staphaureus]

The two compartments are separate. Once K+ channels are open, the difference in concentrations across the membrane is even greater (b/c of the hyperkalemia) thus the membrane potential is increased b/c K+ will have an increased gradient to flow down.

Intracellular is held constant. That is why increasing the gradient effectively increases the membrane potential.

Sorry i'm being thick-headed today and still not getting it.

Assuming that the intracellular K is held at 100 and extracellular K is increased from 0, to 25, to 50... This is expected to increased the membrane potential. However, how is this increasing the membrane potential when more positive charge is added to the extracellular.

The only that it makes sense to me is that since extracellular K+ is added with Cl, and that the membrane is permeable to K+, then a increasing extracellar K+ lead to a decreasing K+ diffusion out of the cell raising the membrane potential.

Other than that, I don't understand why adding a K+ outside the cell actually makes inside the cell more positive.

 

[blz]

The resting membrane potential is pretty much determined by K+ since it has the highest conductance at resting conditions. if you remember our guy nernst he said:

EK = -61 log [K+]i / [K+]o = -96 mV

so let's use your numbers, Ki = 100, Ko = 1 ---> -122mV for our resiting potential

now keep Ki = 100 and Ko = 10 (increasing ECF, hyperkalemia) ---> -61 mV

so you went from -122mv to -61mv and you depolarized that membrane. tada!

so basically that resting membrane potential depends on the concentration difference across the membrane. when you increase the ECF K+ there is smaller driving force and thus less potential diffence (less negative).

 

[Krazykritter]

blz has a good explanation w/ numbers there, but here is what I got this time w/out being a bonehead myself (hopefully).

K+ is normally maintained by a slow passive flow out of the cell driven by the gradient. Add K+ extracellularly depletes this gradient & therefore, less K+ is able to flow out of the cell passively. This leads to an accumulation of K+ intracellularly & a tendency to depolarize more easily.

Sorry for my stupid first post. Hope this helps if numbers don't do it for you.

 

[cdql]

blz has a good explanation w/ numbers there, but here is what I got this time w/out being a bonehead myself (hopefully).

K+ is normally maintained by a slow passive flow out of the cell driven by the gradient. Add K+ extracellularly depletes this gradient & therefore, less K+ is able to flow out of the cell passively. This leads to an accumulation of K+ intracellularly & a tendency to depolarize more easily.

Sorry for my stupid first post. Hope this helps if numbers don't do it for you.

Thanks for the great explanation!

 

[medstu2006]

Can someone please explain this. With intracellular K concentration held constant, increasing extracellular will increase (make more positive) the membrane potential, depolarizing it.

This doesn't make sense to me. Intuitively, I would expect that increasing extracellular K+ would make the intercellular even more negative with reference to the extracelluar.

I can understand that increasing extracellular K+ with freely permable K+ can increase intracellar K --> deplarization, but the question specifically said the intracellular K was held constant. Thanks

K ions usually "leak out" or passively diffuse out of cells down their concentration gradient via open channels. If the extracellular K ion concentration is inc. then it reduces the conc. gradient and fewer K ions diffuse out of the cell, thus depolarizing the cell and making the membrane potential more positive. Hope this helps.

 

[A Nurse]

Hi, I realise this is an old thread, so my post will be useless to staphaureus, but I expect others may stumble on it when trying to understand how potassium changes the cell resting membrane potential (RMP), so will start at the basics and hope this helps.

Equilibrium Potentials

• As ions diffuse across a selectively permeable membrane down their concentration gradients they redistribute the electrical charge across that membrane and create an electrical difference, this is the diffusion potential.
• For example, as K diffuses out of the cell down its concentration gradient, positive charge is lost, and the interior of the cell becomes less positive, or more negative.
• The diffusion potential thus tends to oppose further diffusion of ions, and increases in voltage as diffusion progresses.
• So to use the example, as potassium leaves the cell, the intracellular space becomes progressively more negative, and the diffusion potential and opposition to diffusion progressively increase.
• When the opposing force of the diffusion potential exactly matches the driving force for diffusion due to the concentration gradient, then there is no net movement of ions, the electrical potential at which this occurs is the equilibrium potential (EP).

Resting Membrane Potential

• The cell obviously contains K, Na, Ca, Cl, proteins, and a whole range of other ions, each of which will have its own equilibrium potential.
• The net electrical potential across the cell membrane at rest will thus be the combination of all the equilibrium potentials for each individual ion, and is the resting membrane potential (RMP).
• In other words RMP=(EP k) + (EP Na) + (EP Ca) + (EP Cl) etc etc
• The relative contribution each ion makes to the overall RMP thus depends on the value of its equilibrium potential.
• This in turn depends on the concentration gradient driving diffusion and the relative permeability of the membrane to that ion.
• Cell membranes are far more permeable to potassium than any other ion, so the K equilibrium potential has most influence over the RMP.
• Consequently changes in K equilibrium potential will change the RMP.

Hyperkalaemia and resting membrane potential

• In hyperkalaemia the difference between intra and extracellular potassium concentrations is reduced so the concentration gradient driving diffusion is diminished.
• Thus the opposing negative electrical charge required to balance K diffusion down its concentration gradient is also diminished, and the K equilibrium potential decreases, i.e. becomes less negative.
• Since the EP K determines the RMP, this also becomes less negative and the cell depolarises towards threshold.

Hypokalaemia and resting membrane potential

• In hypokalaemia, the concentration gradient driving diffusion accross the cell membrane increases, since there is a greater difference between the relative K concentrations in each compartment.
• Consequently a larger negative electrical force is required to balance the increased diffusion and the equilibrium potential becomes more negative, i.e. the cell hyperpolarises away from threshold.

Why small changes in potassium alter the RMP so significantly

• The equilibrium potential for any given ion can be calculated using the Nernst equation.
• This states, EP = (-2.3RT/zF)log10 x intracellular/ extracellular conc.
• Although it may look complicated its basically just dividing the intra and extracellular concentrations of an ion and multiplying the result by the log of a constant.
• So the only part of the equation that changes for a given ion, and thus determine changes in the equilibrium potential are the relative intra and extracellular concentrations.
• In previous posts we've been asked to assume that the intracellular concentration of K is held constant at 100.
• For extracellular K concentration lets use the range of 3.5-5.0.
• So with a K of 5, EP K= (constant) x 100/5, or constant x 20
• And at a K of 3.5, EP K= (constant) x 100/3.5, or constant x 28.57
• I don't know the number of the constant for potassium, but the principle is clear that as K falls, so the EP rises and vica versa.
• Thus the EP and consequently the RMP are extremely responsive to extracellular K levels and will change significantly even within the normal range.

I appreciate this is a simplification of the basic principles, but hope it helps someone understand this important topic.

 

[kryptik]

thanks for the thorough explanation A Nurse