An applied depolarization inactivates N152D-K61M, a strongly rectifying, pH-insensitive mutant of Kir1.1, as indicated by a progressive decline in macroscopic inward conductance. The solid bar denotes the time during which voltage was sustained at 70 mV more positive than the resting potentials (Vm) which were −131 ± 5 mV for 0.1 mM external K, −105.9 ± 2 mV for 1 mM external K, and −10.6 ± 2 mV for 75 mM external K. Internal pH was maintained at 7.04 by external acetate buffer at pHo = 7.8. Inward conductance was measured periodically using 20-ms voltage steps to generate momentary inward current during the sustained depolarization.