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

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Abstract

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 α subunit (BKα) in ICs (IC-BKα–KO). Whole cell charybdotoxin–sensitive (ChTX-sensitive) K+ currents were readily detected in control ICs but largely absent in ICs of IC-BKα–KO mice. When placed on a high K+ (HK) diet for 13 days, blood [K+] was significantly greater in IC-BKα–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-BKα–KO CCDs of both sexes. Also, flow-stimulated epithelial Na+ channel–mediated (ENaC–mediated) Na+ absorption was greater in CCDs from female IC-BKα–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-BKα–KO mice.

Authors

Rolando Carrisoza-Gaytan, Evan C. Ray, Daniel Flores, Allison L. Marciszyn, Peng Wu, Leah Liu, Arohan R. Subramanya, WenHui Wang, Shaohu Sheng, Lubika J. Nkashama, Jingxin Chen, Edwin K. Jackson, Stephanie M. Mutchler, Szilvia Heja, Donald E. Kohan, Lisa M. Satlin, Thomas R. Kleyman