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 BK_i and noninactivating (BK_s) 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 BK_i and BK_s current and other RCC currents. The analysis shows that BK current influences both fast hyperpolarization and afterhyperpolarization of single APs and that, consistent with experimental observations, BK_i current facilitates repetitive firing of APs, whereas BK_s current does not. However, the key functional difference between BK_i and BK_s current that accounts for the differential firing is not inactivation but the more negatively shifted activation range for BK_i current at a given [Ca²⁺].