Inhibitory Effects of Dronedarone on Small Conductance Calcium Activated Potassium Channels in Patients with Chronic Atrial Fibrillation: Comparison to Amiodarone

BACKGROUND: Dysfunction of small conductance calcium activated potassium (SK) channels plays a vital role in atrial arrhythmogenesis. Amiodarone and dronedarone are the most effective class III antiarrhythmic drugs. It is unclear whether the antiarrhythmic effect of amiodarone and dronedarone is related to SK channel inhibition. MATERIAL/METHODS: Tissue samples were obtained from the right atria of 46 patients with normal sinus rhythm and 39 patients with chronic atrial fibrillation. Isolated atrial myocytes were obtained by enzymatic dissociation. KCNN2 (SK2) channels were transiently expressed in human embryonic kidney (HEK)-293 cells. SK currents were recorded using whole-cell conventional patch clamp techniques. RESULTS: Amiodarone and dronedarone showed a concentration-dependent inhibitory effect on SK currents (I(KAS)) in atrial myocytes from normal sinus rhythm patients and chronic atrial fibrillation patients. The suppressed efficacy of dronedarone and amiodarone on I(KAS) was greater in atrial myocytes from chronic atrial fibrillation patients than that from normal sinus rhythm patients. Furthermore, in patients with chronic atrial fibrillation, the IC(50) value was 2.42 μM with dronedarone and 8.03 μM with amiodarone. In HEK-293 cells with transiently transfected SK2 channels, both dronedarone and amiodarone had a dose-dependent inhibitory effect on I(KAS). The IC(50) value was 1.7 μM with dronedarone and 7.2 μM with amiodarone in cells from patients with chronic atrial fibrillation. Compared to amiodarone, dronedarone is more efficacy to inhibit I(KAS) and could be a potential intervention for patients with chronic atrial fibrillation. CONCLUSIONS: Dronedarone provides a great degree of I(KAS) inhibition in atrial myocytes from chronic atrial fibrillation than amiodarone. I(KAS) might be a potential target of amiodarone and dronedarone for the management of chronic atrial fibrillation.