Evidence for Functional SK Channels in Isolated Atrial Myocytes

Abstract

Atrial fibrillation (AF) is the most common sustained arrhythmia and contributes to cardiac morbidity and mortality. Extension of the atrial effective refractory period through the block of cardiac potassium channels is a therapeutic strategy for the prevention of re-entrant arrhythmias and AF. However, many conventional potassium channel blockers carry an increased risk of potentially lethal ventricular arrhythmias such as torsades de pointes. Atrial selective compounds may offer attractive therapeutic alternatives. Small-conductance calcium-activated potassium (SK) channels have recently been suggested as a promising atrial selective target for the treatment of AF. Although there is growing evidence for SK channel expression in the mammalian heart, there is little consensus concerning SK function and it is possible that species differences may contribute to the controversy. We have investigated the expression and function of SK channels in atrial myocytes from mouse and rabbit. Immunocytochemistry using confocal microscopy showed the presence of SK2 protein in mouse atrial myocytes, with clear localization of staining along the z-lines. Whole-cell voltage clamp recordings from mouse and rabbit atrial myocytes, using a pipette solution with limited Ca2+ buffering capacity, revealed the presence of apamin-sensitive currents positive to −30 mV. In mouse cells, the apamin-sensitive difference currents slowly decayed during the sustained depolarization. In contrast, a rapidly decaying apamin-sensitive current that inactivated within 50 ms was observed in a proportion of rabbit atrial myocytes . These data suggest that both mouse and rabbit atrial myocytes exhibit functional SK channels, with the presence of SK2 protein confirmed in mouse cells. The apparent kinetic differences of apamin-sensitive current between species may underlie different physiological roles.