TY - JOUR T1 - Effects of Class III Antiarrhythmic Drugs on Transient Outward and Ultra-rapid Delayed Rectifier Currents in Human Atrial Myocytes JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 384 LP - 392 VL - 281 IS - 1 AU - Jianlin Feng AU - Zhiguo Wang AU - Gui-Rong Li AU - Stanley Nattel Y1 - 1997/04/01 UR - http://jpet.aspetjournals.org/content/281/1/384.abstract N2 - A variety of class III antiarrhythmic agents have been shown to block the delayed rectifier current, but their effects on other K+ currents, particularly in human tissues, are less clear. We studied the concentration-dependent actions of the class III compounds d -sotalol, E-4031 and ambasilide on the transient outward current (Ito) and the ultra-rapid delayed rectifier current (IKur) in human atrial myocytes. d -Sotalol and E-4031 failed to alter Ito or IKur at concentrations up to 500 and 50 μM, respectively. In contrast, ambasilide produced a concentration-dependent inhibition of Ito and IKur, with statistically significant effects at 10 μM and maximum effects at 100 μM. The 50% inhibitory concentration of ambasilide averaged 23 ± 2 μM and 34 ± 3 μM for Ito and IKur respectively. Ambasilide did not alter the voltage-dependence of activation or inactivation of Ito, or the voltage-dependence of IKur, and it did not affect Ito recovery from inactivation. On the other hand, ambasilide accelerated Ito inactivation, by introducing a more rapid component that accelerated with increasing drug concentration. Furthermore, block of both Ito and IKur developed over time after the onset of depolarization, with time constants of 5.8 ± 0.8 msec and 2.5 ± 0.4 msec at concentrations of 10 and 50 μM for Ito and 6.1 ± 0.8 msec and 2.1 ± 0.3 msec at 10 and 50 μM for IKur. We conclude that neither d -sotalol nor E-4031 affects Ito or IKur, whereas ambasilide produces efficacious open-channel block of both currents, in human atrial myocytes. The American Society for Pharmacology and Experimental Therapeutics ER -