Caveolin-1 deficiency inhibits the basolateral K+ channels in the distal convoluted tubule and impairs renal K+ and Mg2+ transport

Lijun Wang, Chengbiao Zhang, Xiaotong Su, Dao Hong Lin, Wenhui Wang

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Kcnj10 encodes the inwardly rectifying K+ channel Kir4.1 in the basolateral membrane of the distal convoluted tubule (DCT) and is activated by c-Src. However, the regulation and function of this K+ channel are incompletely characterized. Here, patch-clamp experiments in Kcnj10-transfected HEK293 cells demonstrated that c-Src-induced stimulation of Kcnj10 requires coexpression of caveolin-1 (cav-1), and immunostainingshowed expression of cav-1 in the basolateralmembrane of parvalbumin-positive DCT. Patch-clamp experiments detected a 40-pS inwardly rectifying K+ channel, a heterotetramer of Kir4.1/Kir5.1, in the basolateral membrane of the early DCT (DCT1) in both wild-type (WT) and cav-1- knockout (KO) mice. However, the activity of this basolateral 40-pS K+ channel was lower in KO mice than inWTmice.Moreover, the K+ reversal potential (an indication ofmembrane potential) was less negative in the DCT1 of KO mice than in the DCT1 of WT mice. Western blot analysis demonstrated that cav-1 deficiency decreased the expression of the Na+/Cl- cotransporter and Ste20-proline-alanine-rich kinase (SPAK) but increased the expression of epithelial Na+ channel-α. Furthermore, the urinary excretion of Mg2+ and K+ was significantly higher in KO mice than in WT mice, and KO mice developed hypomagnesemia, hypocalcemia, and hypokalemia. We conclude that disruption of cav-1 decreases basolateral K+ channel activity and depolarizes the cell membrane potential in the DCT1 at least in part by suppressing the stimulatory effect of c-Src on Kcnj10. Furthermore, the decrease in Kcnj10 and Na+/Cl- cotransporter expression induced by cav-1 deficiency may underlie the compromised renal transport of Mg2+, Ca2+, and K+.

Original languageEnglish
Pages (from-to)2678-2690
Number of pages13
JournalJournal of the American Society of Nephrology : JASN
Volume26
Issue number11
DOIs
StatePublished - Nov 2015
Externally publishedYes

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