Cardiac Electrophysiology II: Cardiac Action Potential (Weiss)

Question 1

Gap junction

Answer 1

Gap junction channels form syncytium to electrically couple cardiac cells with low resistance pathway

6 Connexins = Hemichannel = Connexon

2 Hemichannels = Gap junction channel

Question 2

What do T tubules do to conduction velocity?

Answer 2

T tubules SLOW DOWN conduction velocity

Purkinje cells, SA node, AV node, and atrial cells don’t have T tubules because we don’t need these cells to CONTRACT, we need them to conduct AP fast

Question 3

Ventricular/Atrial/His-Purkinje action potential

Answer 3

Phase 0 Upstroke: Voltage-gated Na+ channels open and Na+ comes in

Phase 1 Initial Repolarization: Inactivation of Na+ channels and voltage-gated K+ channels let K+ out.

Phase 2 Plateau: Voltage-gated Ca2+ channels (L-type, on sarcolemma!) let Ca2+ in and that balances K+ out. (this is when RyR let more Ca2+ out and you get contraction!)

Phase 3 Repolarization: Slow voltage-gated K+ channels open and let lots of K+ out (“inward rectifier K+ current”). Also Ca2+ L-type channels close.

Phase 4 Resting potential: Different K+ channels open and get lots of K+ out that way. Also have Na+ and Ca+ coming in to balance it out.

Question 4

SA/AV action potential

Answer 4

Phase 0 Upstroke: T-type voltage-gated Ca2+ open and Ca2+ comes in.

Phase 1 and 2 don’t exist

Phase 3 Repolarization: Ca2+ channels inactivated and K+ channels activated, letting K+ out.

Phase 4 Spontaneous slow diastolic depolarization: I_f (funny channels) Na+ channels open and let Na+ out (this accounts for automaticity of SA and AV nodes, and this slope determines HR)

Question 5

“Voltage clock”

Answer 5

I_f Na+ channels bringing in positive charge to depolarize

Question 6

“Ca2+ clock”

Answer 6

Ca-Na exchanger causes inward + charge at increasingly frequent rate during diastole, causing progressive depolarization to threshold (increasingly frequent spontaneous openings of RyR occur as SR refills during diastole)

Question 7

Do atrial cells have T tubules?

Answer 7

NO!

Because atria don’t REALLY need to contract well. Ventricular filling mostly because of suction created during first 1/3 of diastole when the ventricles relax, and the “atrial kick” is just surplus

Question 8

Beta agonists increase PKA which phosphorylates L-type Ca2+ channels and lets more Ca2+ in (increase I_Ca(L)), but why then don’t they increase AP duration, shorten diastole and compromise blood flow?

Answer 8

Beta agonists also increase outward currents to counteract the inward Ca2+ current:

1) I_Ks is K+ leaving
2) I_Cl(cAMP) is Cl- coming in

Question 9

Myocytes have a high resting K+ conductance (K+ is always going out), but how then do we maintain a high voltage for the plateau of the AP?

Answer 9

Inward rectifier K+ channels (I_K1 and I_KACh) depend on the voltage in the cell!

During plateau, cell is positive and these channels don’t let much K+ out (allow for plateau), then as cell gets more negative, these channels let K+ out to help with repolarization

Positive feedback

Question 10

How is HR regulated by autonomic stimulation?

Answer 10

By modifying:

1) Maximum diastolic potential (more positive “resting” potential during diastole will increase HR): beta agonists upregulate I_Ca(L) and increase HR; ACh on muscarinic agonists downregulate I_Ca(L) and decrease HR; Ach on muscarinic activates I_K(ACh) to hyperpolarize membrane and slow HR
2) Diastolic depolarization rate (increasing the time it takes to spontaneously depolarize during diastole will decrease HR): beta agonists cause SERCA to become leakier, so reach threshold faster
3) AP threshold (increasing threshold will decrease HR; decreasing threshold will increase HR)