NYMC Faculty Publications
L-WNK1 is Required for BK Channel Activation in Intercalated Cells
Author Type(s)
Faculty
Journal Title
American Journal of Physiology. Renal Physiology
First Page
245
Last Page
254
Document Type
Article
Publication Date
8-1-2021
Department
Pharmacology
Abstract
Large-conductance K+ (BK) channels expressed in intercalated cells (ICs) in the aldosterone-sensitive distal nephron (ASDN) mediate flow-induced K+ secretion. In the ASDN of mice and rabbits, IC BK channel expression and activity increase with a high-K+ diet. In cell culture, the long isoform of with-no-lysine kinase 1 (L-WNK1) increases BK channel expression and activity. Apical L-WNK1 expression is selectively enhanced in ICs in the ASDN of rabbits on a high-K+ diet, suggesting that L-WNK1 contributes to BK channel regulation by dietary K+. We examined the role of IC L-WNK1 expression in enhancing BK channel activity in response to a high-K+ diet. Mice with IC-selective deletion of L-WNK1 (IC-L-WNK1-KO) and littermate control mice were placed on a high-K+ (5% K+, as KCl) diet for 10 or more days. IC-L-WNK1-KO mice exhibited reduced IC apical + subapical α-subunit expression and BK channel-dependent whole cell currents compared with controls. Six-hour urinary K+ excretion in response a saline load was similar in IC-L-WNK1-KO mice and controls. The observations that IC-L-WNK1-KO mice on a high-K+ diet have higher blood K+ concentration and reduced IC BK channel activity are consistent with impaired urinary K+ secretion, demonstrating that IC L-WNK1 has a role in the renal adaptation to a high-K+ diet.NEW & NOTEWORTHY When mice are placed on a high-K+ diet, genetic disruption of the long form of with no lysine kinase 1 (L-WNK1) in intercalated cells reduced relative apical + subapical localization of the large-conductance K+ channel, blunted large-conductance K+ channel currents in intercalated cells, and increased blood K+ concentration. These data confirm an in vivo role of L-WNK1 in intercalated cells in adaptation to a high-K+ diet.
Recommended Citation
Ray, E. C., Carrisoza-Gaytan, R., Al-Bataineh, M., Marciszyn, A. L., Nkashama, L. J., Chen, J., Winfrey, A., Griffiths, S., Lam, T. R., Flores, D., Wu, P., Wang, W., Huang, C., Subramanya, A. R., Kleyman, T. R., & Satlin, L. M. (2021). L-WNK1 is Required for BK Channel Activation in Intercalated Cells. American Journal of Physiology. Renal Physiology, 321 (2), 245-254. https://doi.org/10.1152/ajprenal.00472.2020
