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 ro le in defining membrane potential were studied in cultured rat chromaf fin cells. Two variants of large-conductance, Ca2+ and voltage-depende nt 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 ext ent of whole-cell current decay was not explained by differences in cy tosolic [Ca2+] regulation among cells; rather, variation was due to di fferences in the intrinsic properties of the underlying BK channels. A bout 75% of rat chromaffin cells and patches express inactivating BK c urrent (termed BKi) while the remainder express noninactivating BK cur rent (termed BKs). The activation time course of both currents is simi lar, as is the dependence of activation on [Ca2+] and membrane potenti al. However, deactivation of BKi channels is slower than that of BKs c hannels. The functional role of these BK channel variants was studied in current-clamp recordings. Although both BKi and BKs currents contri bute to action potential repolarization, cells expressing BKi current are better able to fire repetitively in response to constant current i njection. Blockade of BKi current by charybdotoxin abolishes this beha vior, showing that afterhyperpolarizations mediated by BKi current are permissive for repetitive firing. Thus, important properties of chrom affin cell membrane excitability are determined by the type of BK curr ent expressed.