Effects of chromanol 293B on transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes

It is unclear whether chromanol 293B, a selective inhibitor of slow component of delayed rectifier K+ current (IKs), may affect other K+ currents in human atrium. With whole-cell patch configuration, we evaluated effects of 293B on transient outward K+ current (Ito1) and ultra-rapid delayed rectifier K+ current (IKur) in isolated human atrial myocytes. It was found that 293B inhibited Ito1 and IKur in a concentration-dependent manner. At 10 μM 293B suppressed Ito1 to 3.4 ± 0.4 from 5.1 ± 0.3 pA/pF (P < 0.01), and IKur to 1.5 ± 0.2 from 2.1 ± 0.3 pA/pF (P < 0.01) at +50 mV. The inhibition of Ito1 and IKur was independent of depolarizing voltage, and the concentration of 50% inhibition was 31.2 μM for Ito1, and 30.9 μM for IKur. 293B blocked Ito1 and IKur with the same concentration range, and the significant effect was observed from the concentration of 1 μM. The maximum inhibitive effect was 88% for Ito1 and 96% for IKur at 250 μM. Voltage dependence of activation and inactivation, and time-dependent recovery from inactivation of Ito1 were not altered by 293B; however, time to peak and time-dependent inactivation of Ito1 was significantly accelerated. The results indicate that 293B significantly inhibits the major repolarization K+ currents Ito1 and IKur in human atrial myocytes.