Differential Regulation of Action Potentials by Inactivating and Noninactivating BK Channels in Rat Adrenal Chromaffin Cells

Large-conductance Ca2+-activated K+ (BK) channels can regulate cellular excitability in complex ways because they are able to respond independently to two distinct cellular signals, cytosolic Ca2+ and membrane potential. In rat chromaffin cells (RCC), inactivating BKi and noninactivating (BKs) channels differentially contribute to RCC action potential (AP) firing behavior. However, the basis for these differential effects has not been fully established. Here, we have simulated RCC action potential behavior, using Markovian models of BKi and BKs current and other RCC currents. The analysis shows that BK current influences both fast hyperpolarization and after hyperpolarization of single APs and that, consistent with experimental observations, BKi current facilitates repetitive firing of APs, whereas BKs current does not. However, the key functional difference between BKi and BKs current that accounts for the differential firing is not inactivation but the more negatively shifted activation range for BKi current at a given [Ca2+].