Outward currents underlying repolarization in human atrial myocytes

OBJECTIVE: The goals of this study were to identify the types of outward potassium (K+) currents that are activated at membrane potentials corresponding to the plateau of the action potential in human atrial myocytes, and to compare their properties with published data describing the K+ channels which have been cloned from a human cDNA library. METHODS: Specimens of right atrial appendages were obtained from patients undergoing cardiac surgery. Single myocytes were isolated enzymatically and whole cell voltage- and current-clamp recording techniques were applied. RESULTS: The outward K+ current in most cells consisted of transient and sustained (non-inactivating) components. 4-Aminopyridine (4-AP, 50 microM) broadened the action potential and increased the plateau height by blocking a Ca(2+)-independent transient outward K+ current (I(t)). The transient and the pedestal components could also be separated by using two pulse voltage-clamp protocols to inactivate them: the transient component was inactivated completely by 400 ms depolarizing pre-pulses (-80 to 0 mV). In contrast, the inactivation of the pedestal component was not complete even when very long (2500 ms) pre-pulses were applied. The time-course of inactivation of the K+ currents in most cells could be described mathematically by the sum of two exponential functions. The faster of the two processes underlying inactivation was voltage-independent for membrane voltages between +10 and +40 mV. The dependence of the recovery kinetics (reactivation) of I(t) on [K+]o was also studied. When [K+]o was reduced from 5.4 to 1.0 mM, reactivation slowed significantly. In a small fraction of atrial cells, a slowly activating delayed rectifier current was also identified. CONCLUSIONS: These results provide additional information concerning the ionic mechanism(s) for early and late repolarization, and they allow findings from electrophysiologically viable human atrial cells to be related to recent information regarding the molecular biology of potassium currents in human heart.