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

Carvedilol is a β- and α1-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 (Ito) and ultra-rapid delayed rectifier K+ current (IKur) in the human atrium. The present study evaluated effects of carvedilol on Ito and IKur in isolated human atrial myocytes by whole-cell patch-clamp recording technique. We found that carvedilol reversibly inhibited Ito and IKur in a concentration-dependent manner. Carvedilol (0.3 μM) suppressed Ito from 9.2 ± 0.5 pA/pF to 4.8 ± 0.5 pA/pF (P < 0.01) and IKur from 3.6 ± 0.5 pA/pF to 1.9 ± 0.3 pA/pF (P < 0.01) at + 50 mV. Ito was inhibited in a voltage-dependent manner, being significantly attenuated at test potentials from + 10 to + 50 mV, whereas the inhibition of IKur was independent. The concentration giving a 50% inhibition was 0.50 μM for Ito and 0.39 μM for IKur. Voltage-dependence of activation, inactivation and time-dependent recovery from inactivation of Ito were not altered by carvedilol. However, time to peak and time-dependent inactivation of Ito were significantly accelerated, indicating an open channel blocking action. The findings indicate that carvedilol significantly inhibits the major repolarization K+ currents Ito and IKur in human atrial myocytes.