Cardiac Physiology help

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imtheman25

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So currently studying cardiology and I am flustered.....The funny current, Phase 4 (slow depolarization) in pacemaker cells I thought occurred solely due the influx of Na+, but UWorld and other sources say its due to the influx of BOTH Na+ and K+. Which one is it? Why would K+want to flow into the cell when Na+/K+ATPase is establishing a gradient that favors otherwise (high K+ concentration intracellular which actually causes a K+ efflux in other cardiac myocytes during phase 4). Also woudnt that cause a rapid accumulation of K+ within the cell? Please help

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Not an expert by any means but here is my understanding:

In Phase 3 of the pacemaker action potential, K+ efflux results in repolarization. Remember that the action potential is cyclic so Phase 4 slow depolarization is next. Phase 4 starts with slow Na+ influx (funny current) which starts to depolarize the membrane. As this Na+ influx occurs, the K+ efflux channels begin to close but don't all close at once. Thus, there is some overlap between Na+ influx and K+ efflux during Phase 4 until all the K+ efflux channels close. Once Na+ influx outnumbers efflux, depolarization starts to occur. Once the membrane potential reaches -50mV, T-type (transient) Ca2+ channels open causing Ca2+ influx. At -40mV (threshold), L-type (long-lasting) Ca2+ open which triggers the action potential to fire.

Long story short, some leftover K+efflux channels are still open from Phase 3 when Phase 4 starts. It is probably a moot point though; what's important to know is that rapid depolarization is due to Ca2+ influx in pacemaker cells whereas Na+ influx is responsible for rapid depolarization in myocardial cells.
 
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Not an expert by any means but here is my understanding:

In Phase 3 of the pacemaker action potential, K+ efflux results in repolarization. Remember that the action potential is cyclic so Phase 4 slow depolarization is next. Phase 4 starts with slow Na+ influx (funny current) which starts to depolarize the membrane. As this Na+ influx occurs, the K+ efflux channels begin to close but don't all close at once. Thus, there is some overlap between Na+ influx and K+ efflux during Phase 4 until all the K+ efflux channels close. Once Na+ influx outnumbers efflux, depolarization starts to occur. Once the membrane potential reaches -50mV, T-type (transient) Ca2+ channels open causing Ca2+ influx. At -40mV (threshold), L-type (long-lasting) Ca2+ open which triggers the action potential to fire.

Long story short, some leftover K+efflux channels are still open from Phase 3 when Phase 4 starts. It is probably a moot point though; what's important to know is that rapid depolarization is due to Ca2+ influx in pacemaker cells whereas Na+ influx is responsible for rapid depolarization in myocardial cells.

Thank you!! Makes sense BUT the literature states there is a K+ INFLUX (not efflux) as well as Na+ influx during Phase 4
 
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Thank you!! Makes sense BUT the literature states there is a K+ INFLUX (not efflux) as well as Na+ influx during Phase 4

Sorry, missed over that in your original post and you are correct that there is both Na+ and K+ influx during phase 4. The reason for K+ influx is beyond my scope of understanding but Na+ influx is the primary contributor to Phase 4 depolarization.
 
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Sorry, missed over that in your original post and you are correct that there is both Na+ and K+ influx during phase 4. The reason for K+ influx is beyond my scope of understanding but Na+ influx is the primary contributor to Phase 4 depolarization.
haha thanks anyways idk if I should let this go..but I like understanding concepts....not memorizing, and I am studying for STEP 1 too.
 
Braunwald seems to back up your findings. good job on catching it.
Don't rely on FA for your go-to source. If UWorld has it, then it is true. Dig into the classic textbooks (online or print) for your understanding if it's that important to you.

Cheers

"Another important inward current is I f , also called the pacemaker or “funny” current. This current is activated by hyperpolarization and is carried by Na+ and K+ . It generates phase 4 diastolic depolarization in the sinoatrial node. I f modulation is one major mechanism whereby beta-adrenergic and cholinergic neurotransmitters regulate cardiac rhythm under physiologic conditions. Catecholamines increase the probability of channel opening by shifting the channel's activation curve to more positive potentials, which leads to increased current availability for the generation of diastolic depolarization and hence steepens its rate. Cholinergic action, in general, exerts the opposite effect. Fish oil depresses I f."

Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, Elsevier; Philadelphia, PA: 10th Edition, 2015, Table 33-3, p. 639.

 
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haha thanks anyways idk if I should let this go..but I like understanding concepts....not memorizing, and I am studying for STEP 1 too.

I wouldn't waste too much time for the purposes of Step 1 but I am like you, I can't brute force memorize unless I understand concepts. May be worth looking into during some down time. It also raises a theoretical question regarding potassium channel blockers for rate control.
 
Funny currents are conducted by HCN channels, which are K+ channel homologs. They are unique in that they are activated at hyperpolarizing potentials, and the fact that they conduct both Na+ and K+ ions. Don't know if that helps you or not, but thought it might give context.


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