Journal article
L-WNK1 is required for BK channel activation in intercalated cells
American journal of physiology. Renal physiology, Vol.321(2), pp.F245-F254
08/01/2021
DOI: 10.1152/ajprenal.00472.2020
PMCID: PMC8424664
PMID: 34229479
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 a-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.
Details
- Title: Subtitle
- L-WNK1 is required for BK channel activation in intercalated cells
- Creators
- Evan C. Ray - University of PittsburghRolando Carrisoza-Gaytan - Icahn School of Medicine at Mount SinaiMohammad Al-Bataineh - University of PittsburghAllison L. Marciszyn - University of PittsburghLubika J. Nkashama - University of PittsburghJingxin Chen - University of PittsburghAaliyah Winfrey - University of PittsburghShawn Griffiths - University of PittsburghTracey R. Lam - University of PittsburghDaniel Flores - Icahn School of Medicine at Mount SinaiPeng Wu - New York Medical CollegeWenHui Wang - New York Medical CollegeChou-Long Huang - University of IowaArohan R. Subramanya - University of PittsburghThomas R. Kleyman - University of PittsburghLisa M. Satlin - Icahn School of Medicine at Mount Sinai
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Renal physiology, Vol.321(2), pp.F245-F254
- Publisher
- Amer Physiological Soc
- DOI
- 10.1152/ajprenal.00472.2020
- PMID
- 34229479
- PMCID
- PMC8424664
- ISSN
- 1931-857X
- eISSN
- 1522-1466
- Number of pages
- 10
- Grant note
- DK038470; DK110332; DK109038; DK054983; DK111542; DK098145; DK119252; P30DK079307 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 08/01/2021
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984359910602771
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