Knockout of the BK ?2 subunit abolishes inactivation of BK currents in mouse adrenal chromaffin cells and results in slow-wave burst activity.

ABSTRACT: 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 ?2 auxiliary subunits (encoded by the kcnmb2 gene) with a tetramer of pore-forming Slo1 ? 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 ?2 subunits to shift the range of BK channel activation. To investigate the role of BK channels containing ?2 subunits, we generated mice in which the gene encoding ?2 was deleted (?2 knockout [KO]). Comparison of proteins from wild-type (WT) and ?2 KO mice allowed unambiguous demonstration of the presence of ?2 subunit in various tissues and its coassembly with the Slo1 ? subunit. We compared current properties and cell firing properties of WT and ?2 KO CCs in slices and found that ?2 KO abolished inactivation, slowed action potential (AP) repolarization, and, during constant current injection, decreased AP firing. These results support the idea that the ?2-mediated shift of the BK channel activation range affects repetitive firing and AP properties. Unexpectedly, CCs from ?2 KO mice show an increased tendency toward spontaneous burst firing, suggesting that the particular properties of BK channels in the absence of ?2 subunits may predispose to burst firing.

SUBMITTER: Martinez-Espinosa PL 

PROVIDER: S-EPMC4178941 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature