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 (I-Ks), may affect other K+ currents in human atrium. With whole-cell patch configuration, we evaluated effects of 293B on transient outward K+ current (I-tot) and ultra-rapid delayed rectifier K+ current (I-Kur) in isolated human atrial myocytes. It was found that 293B inhibited I-tot and I-Kur in a concentration-dependent manner. At 10 muM 293B suppressed I-tot to 3.4 +/- 0.4 from 5.1 +/- 0.3 pA/pF (P < 0.01), and I-Kur to 1.5 +/- 0.2 from 2.1 +/- 0.3 pA/pF (P < 0.01) at +50 mV. The inhibition of I-tot and I-Kur was independent of depolarizing voltage, and the concentration of 50% inhibition was 31.2 muM for I-tot and 30.9 muM for I-Kur. 293B blocked I-tot and I-Kur with the same concentration range, and the significant effect was observed from the concentration of 1 muM. The maximum inhibitive effect was 88% for I-tot and 96% for I-Kur at 250 muM. Voltage dependence of activation and inactivation, and time-dependent recovery from inactivation of I-tot were not altered by 293B; however, time to peak and time-dependent inactivation of I-tot was significantly accelerated. The results indicate that 293B significantly inhibits the major repolarization K+ currents I-tot and I-Kur in human atrial myocytes. (C) 2003 Elsevier Science Ltd. All rights reserved.