Knockout of the BK β2 subunit abolishes inactivation of BK currents in mouse adrenal chromaffin cells and results in slow-wave burst activity

Rat and mouse adrenal medullary chromaffin cells (CCs) express an inactivating BK current. This inactivation is thought to arise from the assembly of up to four beta 2 auxiliary subunits (encoded by the kcnmb2 gene) with a tetramer of pore-forming Slo1 alpha subunits. Although the physiological consequences of inactivation remain unclear, differences in depolarization-evoked firing among CCs have been proposed to arise from the ability of beta 2 subunits to shift the range of BK channel activation. To investigate the role of BK channels containing beta 2 subunits, we generated mice in which the gene encoding beta 2 was deleted (beta 2 knockout [KO]). Comparison of proteins from wild-type (WT) and beta 2 KO mice allowed unambiguous demonstration of the presence of beta 2 subunit in various tissues and its coassembly with the Slo1 alpha subunit. We compared current properties and cell firing properties of WT and beta 2 KO CCs in slices and found that beta 2 KO abolished inactivation, slowed action potential (AP) repolarization, and, during constant current injection, decreased AP firing. These results support the idea that the beta 2-mediated shift of the BK channel activation range affects repetitive firing and AP properties. Unexpectedly, CCs from beta 2 KO mice show an increased tendency toward spontaneous burst firing, suggesting that the particular properties of BK channels in the absence of beta 2 subunits may predispose to burst firing.