Noob question on action potentials and waves of depolarization

[Daitong]

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Hi all,

This may be a dumb question, but when it comes to the spread of depolarizations, what actually happens in the cell, and what happens for it to spread the AP to the next cell?

For example, in the cardiac myocyte- is it that we have an influx of ions (where do they come from?) which results in a series of many action potentials running all along that same cell's membrane and the AP reaches the border to an adjacent cell. But how does it 'pass on' that wave of depol to the next cell?

Is it due to calcium release from the sarcoplasmic reticulum or sodium (but this is generally outside of the cell!) passing through the gap junctions? Where are these ions coming from to initiate the AP in the first place, and how does it pass it on to adjacent cells?

 

[StilgarMD]

An action potential is a dramatic shift in membrane potential that involves a swift depolarization (usually mediated by the flow of Na+ into the cell), and a swift repolarization (usually mediated by the flow K+ out of the cell.) The names Depol and Repol come from a theory about how membranes underwent action potentials, but it turned out not to be true and the name stuck.

First its important to understand Action potentials really describe what is happening at a particular patch of membrane. The ability of an action potential to spread across a cell's surface relies on some membrane having excitable Na+ channels which can be triggered. An action potential can be thought of as a wave of depolarization. You drop a stone in a lake and that creates a ripple that propagates across the water's surface. In a membrane covered in voltage gated Na+ channels, an initial trigger (like a funny current which slowly depolarizes a cell, or a Ligand-gated channel which just needs the right signal [think ACh @ NMJ]) sets off a ripple effect, where sodium ions from one patch diffuse away from where they came in to the surrounding membrane, cause a depolarization there, which then triggers Vg Na+ Ch's to open, leading to more Na+, and the cycle repeats itself until there is no more excitable membrane.

Now specifically for the Myocardium, you can actually think of the entire ventricle as 1 big cell, because the same way Na+ can diffuse to an adjacent patch of membrane, it can diffuse through gap junctions into another cell, triggering an action potential in the membrane of the adjacent cell. In the heart, there is special pacemaker activity via the funny channels which automatically open and create a slow rise to threshold. The pacemaker tissue is also unique in that it's Phase 0 sharp depolarization isn't Na+, its Ca++, which means it does rely on calcium in extracellular fluid to depolarize.

so Tl;dr - Gap Junctions let the sodium current which creates an AP in one cell travel to the next. They are made of Connexins.

 

[worldbeater]

Depolarizations are due to the cell becoming more positive. This happens in every cell in the body except for the atrium and thalamus, which use calcium to become more positive.

Additional points:
-To become more negative (repolarization), its usually due to potassium efflux (moving out of the cell) because potassium channels are the only channels that are always open
-To control any type of atrial arrhythmia, you use a calcium channel blocker. For a ventricle arrhythmia, use a sodium channel blocker.

 

[StilgarMD]

Depolarizations are due to the cell becoming more positive. This happens in every cell in the body except for the atrium and thalamus, which use calcium to become more positive.

Additional points:
-To become more negative (repolarization), its usually due to potassium efflux (moving out of the cell) because potassium channels are the only channels that are always open
-To control any type of atrial arrhythmia, you use a calcium channel blocker. For a ventricle arrhythmia, use a sodium channel blocker.

The Thalamus and the Atria both depolarize through sodium currents. the SA node and AV node use calcium for Phase 0 Depol.

The channels responsible for the Resting membrane potential are not those responsible for the repolarization of an AP. The sharp drop suggests an overpowering conductance, so just to put things in perspective, you'd imagine 100 K-leak channels making up the RMP, 1000 Vg Na Ch's opening to cause Depol, and 1000 Vg K+ Ch's opening to cause Repol. the RMP channels are essentially not there. If the Vg didn't greatly outnumber them, the AP wouldn't be able to achieve the steep slope it has.

Calcium channel blockers are used for Nodal arrhythmias (since the nodes rely on Ca++ to depol) and Rate control of the ventricles in Afib, since in afib the AV node will be maxed out and the ventricles will be going at about 120 Beats/min. Calcium channel blockers slow the AV node down, allowing fewer APs to cross and slowing down the ventricles.

 

[worldbeater]

The Thalamus and the Atria both depolarize through sodium currents.

Sorry don't agree with you, that's not what UWorld says. You won't get a point if you select that as the answer on that type of question.

Calcium channel blockers are used for Nodal arrhythmias (since the nodes rely on Ca++ to depol) and Rate control of the ventricles in Afib, since in afib the AV node will be maxed out and the ventricles will be going at about 120 Beats/min. Calcium channel blockers slow the AV node down, allowing fewer APs to cross and slowing down the ventricles.

Your right. The AV node is located in the atrium (lower right area). Calcium channel blockers block the AV node. The AV node control the ventricular rate. So if you use a calcium channel blocker to block the AV node, the ventricles will slow down.

 

[StilgarMD]

Sorry don't agree with you, that's not what UWorld says. You won't get a point if you select that as the answer on that type of question.

After looking into it, this is what I've come up with:
the Thalamus makes use of T-type (or Transient type) calcium channels - Mutations in these channels give rise to Absence seizures, and why you can use Ethosuximide, Valproate to stop them.
Atria, Ventricles, and the Nodes use L-type (or Long type) calcium channels. These are the targets of calcium channel blockers (both DHP types, which select for these channels in vasculature, and non-DHP types, that selective for them on the heart).

The only mention of T-type channels on Atria comes from Wikipedia, and combing through the reference doesn't seem to pan out what it is being used to back up. For all intents and purposes (i.e. for Step 1), It is safe to ignore their presence on Atria.

"Depolarizations are due to the cell becoming more positive. This happens in every cell in the body except for the atrium and thalamus, which use calcium to become more positive."

The Thalamus may in fact use calcium in certain settings. but the thalamus is made up of neurons which rely on sodium for Phase 0 depolarization, and may reach threshold via T-type calcium channels (more frequently than normal in the case of Absence seizures). The Atria are the muscles, which rely on sodium to become positive, and L-type channels to stay positive (the plateau). Your statement makes no such nuanced claim.

 

[worldbeater]

For all intents and purposes (i.e. for Step 1), It is safe to ignore their presence on Atria.

That's fine if you don't agree with me, but I encourage you to apply your logic to some cardio practice questions and see if you get them correct or not. At the end of the day, that's what matters, for all of us to be getting as many questions correct as possible.

 

[StilgarMD]

That's fine if you don't agree with me, but I encourage you to apply your logic to some cardio practice questions and see if you get them correct or not. At the end of the day, that's what matters, for all of us to be getting as many questions correct as possible.

3 Drugs are used for Absence seizures - Ethosuximide, Valproic acid, and Lamotrigine. In order to have any efficacy against these seizure, it requires T-type calcium channel activity. If T type calcium channels had a significant role in cardiac tissue, you'd expect these drugs to have side effects on relating to the heart.

Ethosuximide - "GI, fatigue, headache, urticaria, Stevens-Johnson syndrome. EFGHIJ—Ethosuximide causes Fatigue, GI distress, Headache, Itching, and Stevens-Johnson syndrome"
Valproic acid - "GI distress, rare but fatal hepatotoxicity (measure LFTs), pancreatitis, neural tube defects, tremor, weight gain, contraindicated in pregnancy"
Lamotrigine - "Stevens-Johnson syndrome"

There is no mention in FA or Wikipedia. the presence of these channels on cardiac tissue is not clinically salient. I think you misunderstood something you read in a UWorld explanation. Atria have L-type calcium channels.