Delayed Rectifier Outward Current and Repolarization in Human Atrial Myocytes

Previous work has suggested that the primary time-dependent repolarizing current in human atrium is the transient outward current (Ito), but interventions known to alter the magnitude of the delayed rectifier current (IK) affect atrial electrophysiology and arrhythmias in humans. To explore the potential role of IK in human atrial tissue, we used the whole-cell configuration of the patch-clamp technique to record action potentials and ionic currents in isolated myocytes from human atrium. A delayed outward current was present in the majority of myocytes, activating with a time constant ranging from 348 +/- 61 msec (mean +/- SEM) at -20 mV to 129 +/- 25 msec at +60 mV. The reversal potential of tail currents was linearly related to log [K+]o with a slope of 55 mV per decade, and fully activated tail currents showed inward rectification. The potassium selectivity, kinetics, and voltage dependence were similar to those reported for IK in other cardiac preparations. In cells with both Ito and IK, IK greatly exceeded both components of Ito (Ito1 and Ito2) within 50 msec of a voltage step from -70 to +20 mV. Based on the relative magnitude of Ito and IK, three types of cells could be distinguished: type 1 (58% [73/126] of the cells) displayed a large Ito together with a clear IK, type 2 (13% [17/126] of the cells) displayed only IK, and type 3 (29% [36/126] of the cells) was characterized by a prominent Ito and negligible IK. Consistent differences in action potential morphology were observed, with type 2 cells having a higher plateau and steeper phase 3 slope and type 3 cells showing a triangular action potential and lesser phase 3 slope compared with type 1 cells. We conclude that IK is present in a majority of human atrial myocytes and may play a significant role in their repolarization and that previously observed variability in human atrial action potential morphology may be partially due to differences in the relative magnitude of time-dependent outward currents.