Referenced in: none

Automatically associated channels: Kir1.1 , Kir4.1 , Kir5.1

Title: Caveolin-1 Deficiency Inhibits the Basolateral K+ Channels in the Distal Convoluted Tubule and Impairs Renal K+ and Mg2+ Transport.

Authors: Lijun Wang, Chengbiao Zhang, Xiaotong Su, Dao-Hong Lin, Wenhui Wang

Journal, date & volume: J. Am. Soc. Nephrol., 2015 Nov , 26, 2678-90

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25848073

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 immunostaining showed expression of cav-1 in the basolateral membrane 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 in WT mice. Moreover, the K(+) reversal potential (an indication of membrane 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 Mg(2+) 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 Mg(2+), Ca(2+), and K(+).