A repolarization‐induced transient increase in the outward current of the inward rectifier K + channel in guinea‐pig cardiac myocytes

1 Outward currents of the inwardly rectifying K + current ( I Kir ) in guinea‐pig ventricular myocytes were studied in the presence of 1 mM intracellular free Mg 2+ using the whole‐cell patch‐clamp technique. 2 During repolarizing voltage steps following a large depolarizing pulse (> 0 mV), outward I Kir increased transiently at voltages positive to the K + equilibrium potential (E K , ‐84 mV for 5.4 mM extracellular [K + ]). The rising phase was almost instantaneous, while the decay was exponential. The decay rate was faster at voltages closer to E K (time constants, 33.9 ± 9.8 and 4.8 ± 1.4 ms at ‐30 and ‐50 mV, respectively). 3 The transient outward I Kir was absent when the preceding depolarization was applied from ‐40 mV. Larger transient currents developed as the voltage before the depolarization was shifted to more hyperpolarized levels. 4 Shift of the depolarizing voltage from > 0 mV to more negative ranges diminished the amplitudes of transient outward I Kir and instantaneous inward I Kir during the subsequent repolarizing steps positive and negative to E K , respectively. Since blockage of I Kir by internal Mg 2+ occurs upon large depolarization, and the block is instantaneously relieved at voltages negative to E K , the rising phase of the transient outward I Kir was attributed to the relief of Mg 2+ block at voltages positive to E K . Transient outward I Kir was absent when intracellular [Mg 2+ ] was reduced to 10 μM or lower. 5 Prolongation of the repolarizing voltage step increased the amplitude of time‐dependent inward I Kir during the subsequent hyperpolarization, indicating the progress of a gating process (presumably the channel block by intracellular polyamine) during the decaying phase of outward I Kir . 6 Progressive prolongation of the depolarizing pulse (> 0 mV) from 100 to 460 ms decreased the transient outward I Kir amplitude during the subsequent repolarizing step due to slow progress of the gating (polyamine block) at > 0 mV. 7 Current‐voltage relations measured using repolarizing ramp pulses (‐3.4 mV ms −1 ) showed an outward hump at around ‐50 mV, the magnitude of which increased as the voltage before the conditioning depolarization (10 mV) was shifted to more negative levels. With slower ramp speeds (‐1.5 and ‐0.6 mV ms −1 ), the hump was depressed at voltages near E K . 8 Our study suggests that the relief of Mg 2+ block may increase outward I Kir during repolarization of cardiac action potentials, and that the resting potential, the level/duration of action potential plateau and the speed of repolarization influence the outward I Kir amplitude. 9 A kinetic model incorporating a competition between polyamine block and Mg 2+ block was able to account for the time dependence of outward I Kir .