Cardiac Action Potentials

Question 1

Explain Phase 0 in a cardiac muscle cell and perkinge cells (fast phase)

Answer 1

Signal that causes the membrane to be less negative causes fast sodium channels to open. Upstroke = sodium. Transient influx of sodium, rapidly depolarizing cell until threshold potential is reached (approximately -70mV.) Deactivated almost immediately after activation -> causes rapid early depolarization of the cell.

Question 2

Explain Phase 1 in fast phase cardiac APs

Answer 2

Brief current of repolarization returns the membrane potential to approximately 0mV. Potassium efflux through a transiently activated potassium channel.

Question 3

Explain phase 2 is fast phase cardiac APs

Answer 3

L-type (long) calcium channels open (begin to open during phase 0 when voltage at about -40mV), leading to a plateou where there is a balance between calcium influx and potassium efflux. THIS calcium triggers release of stored calcium in SR, leading to contraction.

Question 4

Phase 3 of fast phase cardiac APs

Answer 4

calcium channels inactivated, potassium efflux dominates, repolarization of the cell

Question 5

Phase 4 of fast phase cardiac AP’s

Answer 5

resting state. Balance of influx and efflux of potassium leaves muscle cell as a membrane potential of about -90mV

Question 6

Slow cardiac action potential - seen in SA node, AV node and Pacemaker cells

Answer 6

Automaticity. Funny sodium channel is perpetually open, so when the cell is depolarized enough by enough sodium, the cell spontaneously depolarizes.

Phase 0 = one funny Na+ channels leaked enough Na to reach threshold, VG-Ca++ channels open to cause further depolarization. T-type Ca++ channels primarily (upstroke=calcium) Maximum neg voltage of pacemaker cells is -60mV.

Phase 3= calcium channels close, potassium channels open, cause repolarization caused by potassium efflux

Phase 4 = Na+funny open, slowly depolarizing the cell until theshold potential is reached (obviously, unlike in fast phase where its completely flat) This is called the pacemaker current (I f)

Question 7

Absolute refractory period

Answer 7

when a cell is completely unexcitable to new stimulation

Question 8

Effective refractory period

Answer 8

includes the absolute refractory period but extends beyond it to include a short interval of phase 3, during which stimulation produces a localized action potential that is not strong enough to propogate further

Question 9

Relative refractory period

Answer 9

interval during which stimulation triggers an action potential that is conducted but the rate of rise of the AP is slower because some sodium channels are still inactivated.

Question 10

Name the three components of troponin and say what they do

Answer 10

Troponin T -> links the troponin complex to the actin and tropomyosin molecules

Troponin I -> inhibits the ATPase activity of the actin-myosin interaction

Troponin C -> responsible for binding calcium ions that regulate the contractive process. As calcium binds Tropnin C, the activity of Troponin I is inhibited, which exposes binding bite of actin and myosin.

Question 11

What are ryanodine receptors?

Answer 11

Invagination of the T-tubules with L-type calcium channels bring them in close proximity with ryanodine receptors. Calcium binds to the ryanodine receptor which causes a great increase in release of calcium from the SR into the cytosol from the stores in the terminal cirternae. This is called calcium-induced calcium release. (CICR)

Question 12

Myocyte relaxation

Answer 12

Towards the end of phase 2, L-type channels inactivate, arresting the influx of calcium into the cell and abolishing the trigger for CICR. Calcium is pumped back into the SR by SERCA. Calcium that entered the cell through L-type channels gets removed by sarcolemmal Na+/Ca++ echanger and by a lesser extend the Ca++-ATPase pump.

Question 13

Beta adrenergic signaling of the myocardium

Answer 13

Catecholamines bind the myocyte beta 1 adrenergic receptor, which is coupled and activates Gs, which stimulates adenylyl cyclase, which converts ATP into cAMP, which activates protein kinases which phosphorilate some cellular proteins like the L-type calcium channels and the ryanodine receptor. Makes them more twitchy!

ALSO enhances myocyte relaxation because return of calcium from the cytosol is controlled by phospholamban. Phospholamban inhibits calcium uptake by SERCA when its dephosphorylated. Also it phosphorylates TnI, inhibiting actin-myocin interaction and promoting quick muscle relaxation.

Question 14

Cholinergic signaling via sympathetic inputs and the heart

Answer 14

Opposes effects of beta adrenergic stimulation

AcH binds to muscarinic M2 receptors, activates Gi proteins, which inhibit adenylate cyclase.