L-WNK1 is required for BK channel activation in intercalated cells
| Autor: | Allison L. Marciszyn, Tracey Lam, Lubika J. Nkashama, Daniel Flores, Rolando Carrisoza-Gaytán, Mohammad M. Al-bataineh, Shawn E. Griffiths, Arohan R. Subramanya, Jingxin Chen, Thomas R. Kleyman, Evan C. Ray, Aaliyah Winfrey, Chou Long Huang, Peng Wu, Wen-Hui Wang, Lisa M. Satlin |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Gene isoform BK channel Physiology 030232 urology & nephrology Kidney Excretion Mice 03 medical and health sciences 0302 clinical medicine WNK Lysine-Deficient Protein Kinase 1 Animals Intercalated Cell Secretion Large-Conductance Calcium-Activated Potassium Channels Ion Transport biology Chemistry Kinase Nephrons WNK1 Molecular biology BK channel activity 030104 developmental biology Potassium biology.protein Research Article |
| Zdroj: | Am J Physiol Renal Physiol |
| ISSN: | 1522-1466 1931-857X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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