Effects of flecainide, quinidine, and 4-aminopyridine on transient outward and ultrarapid delayed rectifier currents in human atrial myocytes.

摘要: Antiarrhythmic drugs prevent atrial reentrant arrhythmias by prolonging action potential duration and refractoriness. The ionic mechanisms which antiarrhythmic alter human repolarization are poorly understood. present study was designed to assess the concentration-, voltage-, time- frequency-dependent effects of agents quinidine flecainide, as well K+ channel blocker 4-aminopyridine, on calcium-independent transient outward current (Ito1) ultrarapid delayed rectifier (IKur) in isolated myocytes. Quinidine flecainide blocked Ito1 at clinically relevant concentrations. Block use frequency dependent, whereas block independent, 4-aminopyridine showed use-dependent unblocking. Depolarizing prepulses enhanced reduced a fashion suggesting preferential interaction with inactivated state for resting, closed 4-aminopyridine. depended depolarizing test pulse open block. All three accelerated inactivation during depolarization 1 Hz failed initial rise, appearing time constants 6.3 +/- 1.2 msec 14.5 4.2 3.0 0.9 16 degrees C, role opening development. IKur clinical concentrations, had no effect IKur. voltage part dependence attributable open-channel remainder compatible blocking site within field position subject 23% total electrical field. Quinidine's actions were similar those previously reported cardiac clone Shaker family (Kv1.5), is believed be equivalent native current. These results indicate that Ito1, blocks IKur, myocytes state-dependent fashion. Because drug manifest have been shown potentially important currents repolarization, these findings understanding underlying properties drugs.