Effects of carvedilol on transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes

Abstract Carvedilol is a β- and α 1 -adrenoceptor antagonist. It is widely used in the treatment of cardiovascular diseases including atrial arrhythmias. However, it is unclear whether carvedilol may affect the repolarization currents, transient outward K + current ( I to ) and ultra-rapid delayed rectifier K + current ( I Kur ) in the human atrium. The present study evaluated effects of carvedilol on I to and I Kur in isolated human atrial myocytes by whole-cell patch-clamp recording technique. We found that carvedilol reversibly inhibited I to and I Kur in a concentration-dependent manner. Carvedilol (0.3 μM) suppressed I to from 9.2 ± 0.5 pA/pF to 4.8 ± 0.5 pA/pF ( P I Kur from 3.6 ± 0.5 pA/pF to 1.9 ± 0.3 pA/pF ( P I to was inhibited in a voltage-dependent manner, being significantly attenuated at test potentials from + 10 to + 50 mV, whereas the inhibition of I Kur was independent. The concentration giving a 50% inhibition was 0.50 μM for I to and 0.39 μM for I Kur . Voltage-dependence of activation, inactivation and time-dependent recovery from inactivation of I to were not altered by carvedilol. However, time to peak and time-dependent inactivation of I to were significantly accelerated, indicating an open channel blocking action. The findings indicate that carvedilol significantly inhibits the major repolarization K + currents I to and I Kur in human atrial myocytes.