Electrophysiology question

[whatzcool]

How does calcium increase the threshold potential (ie, make it less negative) and thus reduce firing of a heart muscle cell?

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[VCU07]

The release of calcium from the SR should depolarize the cells and thus make them more negative eventually leading to an action potential. This should increase the firing rate and cause muscle contraction. You must remember that the heart is myogenic (although it can still be under sympathic and parasympathetic control). There are two mechanisms by which the APs are generated in the SA node and then another, different mechanism by which the APs are generated in the AV Node, Purkinje Fibers, and Ventricular Fibers. The only way I can think of to decrease the Heart contraction if by activating the parasyms.

 

[VCU07]

Sorry, there are other ways to reduce firing of heart muscles cells. I just gave you one example.

 

[punjabiMD]

The release of calcium from the SR should depolarize the cells and thus make them more negative eventually leading to an action potential. This should increase the firing rate and cause muscle contraction. You must remember that the heart is myogenic (although it can still be under sympathic and parasympathetic control). There are two mechanisms by which the APs are generated in the SA node and then another, different mechanism by which the APs are generated in the AV Node, Purkinje Fibers, and Ventricular Fibers. The only way I can think of to decrease the Heart contraction if by activating the parasyms.

dude:
Increasing intracellular Ca increases the potential (more POSITIVE... if you make a cell more negative you will hyperpolarize it and make it harder to trigger an AP) thereby increasing the excitability of the cell; therefore it becomes easier to trigger an action potential. This is one of the HUGE reasons that CA channel blockers are so widely used for things like coronary vasospasm and also, just as important, the vasospasm that occurs after a subarachnoid hemorrhage (which is the leading cause of delayed morbidity/death in these patients). For the most part (this is a huge generalization) the AP upstroke in the SA and AV nodes is slowly brought on by the Ca influx; in the rest of the atrial and ventricular muscle and in the His-Purkinje system, the AP is brought on rapidly by the Na influx.

 

[punjabiMD]

How does calcium increase the threshold potential (ie, make it less negative) and thus reduce firing of a heart muscle cell?

oh yeah, so Ca increase does not reduce firing of a heart muscle cell... could you please describe where you may have read this?

 

[VCU07]

I agree with the previous post...I mistyped my answer....sorry! (i meant less neg., not more neg.) I also would like to know where you have read about the whole Ca story.

 

[whatzcool]

It's from Brenner & Rector's The Kidney, 7th ed page 1022.

Intravenous calcium is the first-line drug in the emergency management of hyperkalemia. The mutually antagonistic effects of Ca2+ and K+ on the myocardium and the protective role of Ca2+ in hyperkalemia have long been known. Calcium raises the action potential threshold and reduces excitability without changing the resting membrane potential. By restoring the difference between resting and threshold potentials, Ca2+ reverses the depolarization blockade due to hyperkalemia.

So, people use Ca to treat hyperkalemia, but what makes Ca to raise threshold instead of resting membrane potential?

 

[VCU07]

I have never heard of such an event...but maybe I am wrong (or just have not learned about it yet)?

 

[punjabiMD]

I looked and I looked and I looked. The mechanism written in "The Kidney" was also repeated in eMedicine. However, I could not find any mechanism by which Ca increases threshold and decreases excitability. Is there an electrophysiologist in the house?

This is my take:
hyperkalemia initially causes partial depolarization. This prolonged depolarization actually decreases excitability of the cell.
Hypercalcemia (which is also a side effect of some of the cardiac glycosides)predisposes to EADs (early after-depolarizations; these are depolarizations that occur during phase 2 or phase 3 of the action potential).
So, maybe the EAD mechanism helps to re-establish excitability to the cell.

 

[proman]

According to Cecil's, the extracellular K interacts with the extracellular domain of the sodium channels. There's a segment of the sodium channel that is somewhat anionic. Increasing the outside [Ca] "screens" this domain. I think it's probably due to the difference in effective ionic size between Ca and K. Regardless, the interaction with Ca doesn't block the sodium flux, whereas the interaction with K does.

Also, I think the restoration of the negativity of the membrane potential comes from the gradient between intracellular (almost no free Ca) and extracellular (much larger concentration of Ca).

I also haven't found this written anywhere in one complete explanation. The above is a compilation of what I found. Hope this helps.

 

[Kalel]

I just looked this up on uptodate.com. High extracellular potassium depolarizes cardiac myocytes and inactivates sodium channels which will decreasing membrane excitability (which I think is similar to "threshold potential" on a cellular level). This leads to a bunch of electrophysiological changes that can be seen on ECG (eg peaked T waves, loss of a P wave, eventual sine wave, asystole/death). Calcium is thought to antagonize the membrane effect of hyperkalelmia, but the exact mechanism isn't well understood. If anyone asks you what the mechanism of using calcium therapy in hyperkalemia within the hospital (eg in a clinical setting) though, the only answer that they are looking for is that "it stabilizes the cell membrane". It's a common pimping question that only has a poorman's clinical explanation. The other therapies for hyperkalemia (eg diuretics, insulin with glucose, kayexalate, and dialysis) have better understood mechanisms (ie removing potassium from the extracellular area), but calcium is still first line therapy with emergent hyperkalemia even though it does nothing to the actual extracellular potassium concentration.