Modulation of voltage-dependent inactivation of the inwardly rectifying K+ channel by chloramine-T

Abstract The inwardly rectifying K + channel ( I K 1 ) exhibits voltage-dependent inactivation at membrane voltages more negative than ∼-140 mV. The effect of chloramine-T on the inactivation of I K 1 was examined in guinea-pig ventricular myocytes using the patch-clamp technique. Chloramine-T (2 mM) irreversibly inhibited the time-dependent decay of whole-cell I K 1 inactivation. As a result, the negative slope region of the current-voltage (I–V) relationship was abolished. In cell-attached single channel recordings, the number of active channels in the patch decreased with time during the voltage-clamp step to the K + equilibrium potential ( E K ) of -100 mV. Chloramine-T prevented this time-dependent decrease in channel number, and ensemble averaged currents exhibited abolishment of time-dependent decay of channel activity at E K -100 mV . These results suggest that the hyperpolarization-induced inactivation of cardiac I K 1 is controlled by voltage-dependent intrinsic gating.