An applied depolarization inactivates N152D, a strongly rectifying, pH-insensitive mutant of Kir1.1, as indicated by a progressive decline in macroscopic inward conductance. The solid bar denotes application of a sustained voltage 100 mV more positive than the resting potentials (Vm), which were −107 ± 2 mV for 1 mM external K, −71.9 ± 2 mV for 10 mM external K, and −8.9 ± 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.