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

The inwardly rectifying K+ channel (IK1) exhibits voltage-dependent inactivation at membrane voltages more negative than approximately -140 mV. The effect of chloramine-T on the inactivation of IK1 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 IK1 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 (EK) 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 EK -100 mV. These results suggest that the hyperpolarization-induced inactivation of cardiac IK1 is controlled by voltage-dependent intrinsic gating.