A 45-year-old man comes to the clinic due to recurrent palpitations accompanied by chest discomfort and shortness of breath. A year ago, he was diagnosed with paroxysmal atrial fibrillation treated with rate control using a beta blocker. Past medical history is also significant for hypertension and obesity. Echocardiogram shows left atrial enlargement, normal left ventricular ejection fraction, and no significant valvular disease. 24-hour Holter monitoring reveals bursts of atrial fibrillation associated with the patient's symptoms. He is initiated on dofetilide to maintain normal sinus rhythm. This medication exerts its main effect on which portion of the action potential curve?

Question

A 45-year-old man comes to the clinic due to recurrent palpitations accompanied by chest discomfort and shortness of breath.  A year ago, he was diagnosed with paroxysmal atrial fibrillation treated with rate control using a beta blocker.  Past medical history is also significant for hypertension and obesity.  Echocardiogram shows left atrial enlargement, normal left ventricular ejection fraction, and no significant valvular disease.  24-hour Holter monitoring reveals bursts of atrial fibrillation associated with the patient's symptoms.  He is initiated on dofetilide to maintain normal sinus rhythm.  This medication exerts its main effect on which portion of the action potential curve?

Quizplus · Accepted Answer

11ec160b_3b7b_99bf_9249_fbb128597229_MD0001_00 The typical myocardial action potential of "nonpacemaker" or cardiac myocytes includes several phases: Phase 0 (rapid depolarization) - occurs when the resting membrane potential reaches threshold; it is characterized by rapid sodium entry into the cell due to activation and opening of voltage-dependent sodium channels. Class I antiarrhythmic drugs (eg, procainamide, flecainide, lidocaine) block these sodium channels and inhibit the initial depolarization phase (phase 0) of the action potential. Phase 1 (early repolarization) - caused primarily by activation of transient outward potassium currents along with a rapid decline in inward sodium current. This phase is not modulated to an appreciable extent by antiarrhythmic medications. Phase 2 (plateau phase) - Stable membrane potential due to a balance of "late" inward calcium current and outward potassium current. Calcium channel blockers (verapamil, diltiazem) are class IV antiarrhythmic drugs that inhibit the L-type calcium channels during this phase. These medications slow the sinus rate, prolong conduction through the atrioventricular node, and depress myocardial contractility (negative inotropic effect). Phase 3 (late repolarization) - characterized by the opening of potassium channels and the efflux of potassium ions from the cell (delayed rectifier potassium currents IKr and IKs) in conjunction with the decay of inward calcium current. Class III antiarrhythmic drugs (amiodarone, sotalol, dofetilide) predominantly block potassium channels and inhibit the outward potassium current during this phase, leading to prolongation of repolarization, action potential duration, and the QT interval on ECG. These medications are often used for maintenance of sinus rhythm in patients with paroxysmal atrial fibrillation. Phase 4 (recovery) - normal resting membrane potential is between −80 and −95 mV and is generated by open potassium channels (inward rectifier current). Antiarrhythmic drugs do not affect phase 4 of the myocyte action potential, but beta blockers and calcium channel blockers can slow diastolic depolarization (phases 4 and 0) in pacemaker cells by decreasing the slope of depolarization. Educational objective: Class III antiarrhythmic drugs (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.

A 45-Year-Old Man Comes to the Clinic Due to Recurrent