Intercalated cell BKα subunit is required for flow-induced K+ secretion.

BK channels are expressed in intercalated cells (ICs) and principal cells (PCs) in the cortical collecting duct (CCD) of the mammalian kidney and have been proposed to be responsible for flow-induced K+ secretion (FIKS) and K+ adaptation. To examine the IC-specific role of BK channels, we generated a mouse with targeted disruption of the pore-forming BK a subunit (BKa) in ICs (IC-BK alpha-KO). Whole cell charybdotoxin-sensitive (ChTX-sensitive) K+ currents were readily detected in control Its but largely absent in ICs of 1C-BK alpha-KO mice. When placed on a high K+ (HK) diet for 13 days, blood [K+] was significantly greater in 1C-BK alpha-KO mice versus controls in males only, although urinary K+ excretion rates following isotonic volume expansion were similar in males and females. FIKS was present in microperfused CCDs isolated from controls but was absent in IC-BK alpha-KO CCDs of both sexes. Also. flow-stimulated epithelial Na+ channel-mediated (ENaC-mediated) Na+ absorption was greater in CCDs from female IC-BK alpha-KO mice than in CCDs from males. Our results confirm a critical role of IC BK channels in FIKS. Sex contributes to the capacity for adaptation to a HK diet in IC-BK alpha-KO mice.