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The recorded action potential shows the typical profile of non-pacemaker cardiac cells, which includes the following phases:

1. Phase 0 (rapid depolarization) – occurs when the resting membrane potential reaches threshold; is characterized by rapid sodium entry into the cell due to activation and opening of voltage-dependent sodium channels.
2. Phase 1 (early repolarization) – caused primarily by activation of transient outward potassium currents along with a rapid decline in inward sodium current.
3. Phase 2 (plateau phase) – stable membrane potential due to a balance of late inward calcium current (L-type channels) and outward potassium current.
4. Phase 3 (late repolarization) – characterized by the opening of additional potassium channels (delayed-rectifier potassium currents) and continued efflux of potassium ions from the cell; this is in conjunction with the decay of inward calcium current.
5. Phase 4 (resting) – normal resting membrane potential is between −80 mV and −95 mV, and it is generated by outward potassium flow through potassium leak channels open at rest.  The Na⁺-K⁺-ATPase pump allows the potassium and sodium gradients to be maintained across the membrane.

The ion flow graph after drug A administration shows a decrease in outward potassium flow from the myocyte during phase 3 repolarization of the myocardial action potential.  Class III antiarrhythmic drugs (eg, amiodarone, sotalol, dofetilide) predominantly block potassium channels and inhibit the outward potassium currents during phase 3 of the cardiac action potential, thereby prolonging repolarization and total action potential duration.

(Choice A)  Adenosine stimulates A1 receptors on the surface of cardiac cells, activating potassium channels and increasing potassium conductance, which causes the membrane potential to remain negative for a longer period.  This results in transient slowing of the sinus rate and increased atrioventricular (AV) nodal conduction delay.

(Choice B)  Digoxin inhibits the Na⁺-K⁺-ATPase pump in myocardial cells, resulting in an increase in intracellular sodium, which leads in turn to a rise in intracellular calcium concentration.  Digoxin does not affect potassium channels and has minimal effect on potassium efflux from myocardial cells during the action potential.

(Choice D)  Esmolol is a rapid-acting, short-duration beta blocker (class II antiarrhythmic) that slows the rate of discharge of sinus or ectopic pacemakers and increases the refractory period of the AV node.  It has no effect on potassium efflux from myocardial cells.

(Choices E, F, and G)  Class IA (procainamide, quinidine), IB (lidocaine), and IC (flecainide) antiarrhythmic drugs inhibit sodium-dependent (phase 0) depolarization and slow conduction.  Class IA and IC agents also have some potassium-blocking activity and can cause prolongation of the action potential (seen mostly with class IA agents).  However, all class I drugs have prominent sodium channel-blocking activity, which would blunt the blue tracing in the above graph.

(Choice H)  Calcium channel blockers (eg, verapamil, diltiazem) inhibit the L-type calcium channels during phase 2 of the myocardial action potential and phase 0 of the pacemaker action potential.  They slow the sinus rate, prolong conduction through the AV node, and depress myocardial contractility.

Educational objective:
Class III antiarrhythmic drugs (eg, amiodarone, sotalol, dofetilide) predominantly block potassium channels and inhibit the outward potassium currents during phase 3 of the cardiac action potential, thereby prolonging repolarization and total action potential duration.