Cell‐Specific Regulation of BK Channel and WNK Kinases in Cortical Collecting Duct (CCD) by Dietary K

Abstract

WNK kinases regulate Na absorption and K secretion in the distal nephron (DN) in response to dietary K intake. Evidence now suggests that WNKs regulate apical BK channel expression; specifically, WNK4 inhibits BKα by targeting the channel for degradation through an ubiquitin‐dependent pathway. Although WNK1 and WNK4 show distinct subcellular distribution patterns, cell‐specific regulation by dietary K has not been studied. Thus, CCDs from NZW rabbits fed a high (HK) or low (LK) K diet for 10 d were fixed, perfused with antibodies (Abs) against BKα, L‐WNK1 (ex. 1) or WNK4 (+ fluorescent 2o Abs), or rhodamine‐peanut lectin (PNA), which binds to apical surfaces of intercalated (IC) but not principal (PC) cells, and examined by confocal microscopy. In LK CCDs, BKα localized predominantly to cilia with minimal detection along the apical membranes of ciliated > non‐ciliated cells. In HK CCDs, apical BKα was enhanced in non‐ciliated > ciliated cells. WNK1 was not detected in LK CCDs (2) but was observed in HK CCDs (4) in a basolateral (BL) distribution in all cells and robustly along the apical membrane of PNA+ cells. In contrast, cytoplasmic and BL WNK4 was observed in all cells in LK CCDs (2) but was minimally expressed in a BL distribution in non‐ciliated cells in HK CCDs (2). In sum, adaptation to a HK diet includes an increase in apical BKα and L‐WNK1 and reduction in WNK4 expression in ICs, suggesting that increased L‐WNK1 and reduced WNK4 contribute to enhanced BK channel‐mediated K secretion in HK animals. In PCs, HK diet increases apical but not cilia BKα, a response associated with BL WNK1 but absent WNK4. These results are consistent with cell‐specific regulation of BKα and WNK kinase expression by dietary K in the DN.