Inactivating and noninactivating Ca²⁺- and voltage-dependent K⁺ current in rat adrenal chromaffin cells

The properties of Ca²⁺- and voltage-dependent K⁺ currents and their role in defining membrane potential were studied in cultured rat chromaffin cells. Two variants of large-conductance, Ca²⁺ and voltage-dependent BK channels, one noninactivating and one inactivating, were largely segregated among patches. Whole-cell noninactivating and inactivating currents resulting from each of these channels were segregated among different chromaffin cells. Cell-to-cell variation in the rate and extent of whole-cell current decay was not explained by differences in cytosolic [Ca²⁺] regulation among cells; rather, variation was due to differences in the intrinsic properties of the underlying BK channels. About 75% of rat chromaffin cells and patches express inactivating BK current (termed BK_i) while the remainder express noninactivating BK current (termed BK_s). The activation time course of both currents is similar, as is the dependence of activation on [Ca²⁺] and membrane potential. However, deactivation of BK_i channels is slower than that of BK_s channels. The functional role of these BK channel variants was studied in current-clamp recordings. Although both BK_i and BK_s currents contribute to action potential repolarization, cells expressing BK_i current are better able to fire repetitively in response to constant current injection. Blockade of BK_i current by charybdotoxin abolishes this behavior, showing that afterhyperpolarizations mediated by BK_i current are permissive for repetitive firing. Thus, important properties of chromaffin cell membrane excitability are determined by the type of BK current expressed.