Hi Dr. Jones,
Awesome, monograph on Hyperkalemia!
I had a question and needed some further clarification regarding the following statement ‘Therefore, at this time it appears that the benefit of administering IV calcium to patients with hyperkalemia is due to enhanced conduction through the L-Type calcium channels and not due to membrane stabilization.’
I’m not totally clear on what you mean by enhanced conduction through the L-Type calcium channels? Do you mean enhanced movement of calcium into the cell? or some else which achieves depolarization.
Thanks Dave 🙂
Thanks for the feedback.
During Phase 0 depolarization, the L-type Ca++ channels begin to open around -60 mV and Ca++ starts to enter the cell – even while all the Na+ is rushing in. This is not meant to initiate an action potential – the heart is preparing for excitation-contraction coupling! It has almost no effect on depolarization as far as we are able to see on the ECG tracing. Now, let me put something in perspective. While the Na+ channels are referred to as the “fast” channels and the Ca++ channels as the “slow” channels (the same ones used by the SA and AV nodes) – the Ca++ channels really aren’t all THAT slow – at least from our perspective. Those L-type Ca++ channels are the same ones that initiate the sinus impulse (up to 150+ beats/minute!) and carry the impulse through the AV node. They are also the ones that prolong Phase 2 to allow Ca++ entry to help trigger myocardial contraction. And they are QUITE capable of initiating an action potential in regular myocardial cells (His-Purkinje and regular working myocytes). It’s just that normally they don’t HAVE to!
Now picture this: a rise in extracellular potassium has reduced the resting membrane potential (i.e., moved it UP the scale closer to 0 mV) to the point that the Na+ channels are no longer effective. But it does not have that same effect on the L-type Ca++ channels. By increasing the extracellular Ca++, we stimulate the L-type channels to increase the Ca++ current and achieve threshold for ALL the heart’s cells.
So, to answer your question, by “enhanced conduction through the L-Type calcium channels,” I mean enhanced movement of Ca++ into the cell. The same action potential that is being initiated in the SA and AV nodes is now being initiated in conducting tissue and working myocardium. Recall that the SA and AV nodes are among the very last tissues in the heart to succumb to hyperkalemia, so those L-type Ca++ channels are very resistant.
And very importantly, you can also see from this that giving Ca++ is just “buying time.” You can keep giving Ca++ IV without much problem but it has ZERO effect on the K+ level – it just allows the heart to keep working in spite of the high K+ level. You still need to get that K+ level DOWN by other means (glucose, insulin, albuterol, etc.).
Hope this helps.
Jerry W. Jones, MD FACEP FAAEM
I am following the reasoning that adding Ca++ extracellularly increases the voltage difference across the membrane, which should then give the Na+ channels an opportunity to reset and be available for activation. I’m getting a little hung up on the state of the channels during the period in which “fewer and fewer are available to be depolarized” and thought it might be helpful to include a brief description of the conformation of the in/activation gates and the voltages they change at:
At allow Na+ channels to de-inactivate–> our cell can now fully depolarize.
If Ca++ is allowed to enter the cell via L-type channels, wouldn’t this once again decrease our membrane potential difference, making it less negative, causing some but not all Na+ channels to depolarize, and resulting in the stunned myocyte dilemma we saw in the beginning?
I see your point in the piece about Ca++ giving us some time to work but that it is limited, I apologize if I’ve just reiterated that point and overcomplicated it!
Thank you vbery much for your very thoughtful comment and for your interest in my website!
I understand what you are saying and it tells me that you are interpreting ECGs at a very sophisticated level (or else that you are a cardiac physiologist operating at a very high level).
There are two things that you may be overlooking here:
While a slowly increasing extracellular K+ level does open then lock (about 1 msec later) Na+ channels making them unavailable to an action potential, it does not have the same effect on Ca++ channels whose threshold is somewhere between -60 Mv and -30 mV (depending on who you read). Giving a bolus of Ca++ will activate the cells because the Ca++ channels are still available. You must understand that, during a normal action potential, just reaching threshold is not enough to activate the cell – the threshold must be reached very, very rapidly (remember that Phase 0 of the action potential is dV/dT; as dV decreases it takes longer and longer to reach threshold). That’s why a slowly rising extracellular K+ level can close Na+ channels without triggering an action potential. And that is also why activation of the L-type Ca++ channels by a Ca++ bolus is effective – because the entrance of Ca++ into the cell is rapid enough to support an action potential. We read about the “fast” Na+ channels and the “slow” Ca++ channels, but don’t lose your perspective: although the Ca++ channels are slower than the Na+ channels, they are still very fast!
I chose not to discuss the specifics of the activation gates because I focus more on clinical issues. I’ve always found that understanding a concept keeps you from having to memorize it.
I’m sorry if I’ve mis understood. It sounds as if the Calcium Glucanate works by essentially boosting the efficiency of the pacing conduction mechanism/ “wiring” of the heart in order to counter balance the “interference” caused by decreasing the action potentials in the other pathways. I find my self wondering if this might work as a more benign option in atrial fibulation scenarios than cardioversion. Sincerely Craig Shuman RRT-ACCS
Hello Craig. Sorry about the delay.
What you need to remember here is that while regular, working myocytes normally depolarize by a sudden influx of Na+ ions through the Na+ channels, they can also depolarize via Ca++ influx through the L-type Ca++ channels – just like the SA node and AV node. The only time this is going to happen, however, is when the Na+ channels are made inactive by a decreasing resting membrane potential such as that caused by a rising extracellular K+ concentration. By “boosting” with extra Ca++, depolarization of the Purkinje fibers and working myocytes via the Ca++ channels is facilitated. This would not be appropriate treatment for atrial fib where the problem is not an inability to depolarize but rather a disorganization of depolarizations resulting in multiple sites of reentry.
Just want to thank you for this great explanation of L channels in myocardial contraction. I wonder if you might comment on a major trend in cardiac surgery, the use of DelNido formulation cardioplegia. DelNido is the name of the surgeon who started its use in pediatric heart surgery. The cardioplegia trend in the 90’s and 2000’s was ever reduced crystalloid, to increase the buffering effects of “Blood” cardioplegia with high ratios of blood to crystalloid, and reduce cellular edema. The main difference is instead of depolarizing the myocardium with K+, DelNido hyperpolarizes the myocardium with lidocaine, and is mostly crystalloid and about 25% blood. It still delivers a large dose of potassium, but not like BCP. It really arrests the heart, for about an hour on one large dose. Its saves a lot of time because of the logistics of giving cardioplegia and de-airing, running etc. But it’s a mystery if its better. People have said that you’re anaerobic, but there is minimal to no oxygen delivery at the temperatures we give blood cardioplegia, so crystalloid actually delivers more oxygen in solution, which would be an arguement for DelNido. It’s only recommended for valve surgery for now, but its rapidly taking over off label, and people are using it for CABG. The other issue I would welcome a comment on…. we sometimes have hyperkalemia problems after many liters of blood cardioplegia. Normally this is given ice cold. Surgeons are very eager to remove the aortic cross-clamp as soon as possible to re-establish blood flow to the ischemic heart. Also because they don’t want reputation for long XC times. So after many liters of cold Hi-K+ cardioplegia, we might run 300-500 of warm cardioplegia to warm the heart up and surgeons are tapping their feet, eager to get the clamp off. IMO, it’s not nearly enough. I want to know if my thinking is wrong though. I find On-Bypass times are often extended 15-30 minutes while we give repeated doses of lidocaine, amiodarone, pace and defibrillate, waiting for the EKG to get right. We had a patient who required dozens of defibs over an hour once. I suggested we re-arrest with high K+ warm blood, and then run warm blood until he restarted, then take the clamp off. This worked. So I would like your understanding to better explain my thoughts on this matter. My hypothesis being that the heart IS getting re-perfused with warm cardioplegia, and we should consider the “clamp off” at the point we start giving the “hot shot”. That we get better outcomes by making sure the endocardium and nodes are fully warm before unclamping. The body is warm, but the heart is often still cold. By running a longer hot shot, the heart is not forced to contract and re-establish metabolism while it’s conduction system is not ready. I wonder if you might have some comment about this at the cellular level.
Sorry, but that’s out of my field. Thanks for commenting.
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