PT - JOURNAL ARTICLE AU - Wang, Lijun AU - Zhang, Chengbiao AU - Su, Xiaotong AU - Lin, Dao-Hong AU - Wang, Wenhui TI - Caveolin-1 Deficiency Inhibits the Basolateral K<sup>+</sup> Channels in the Distal Convoluted Tubule and Impairs Renal K<sup>+</sup> and Mg<sup>2+</sup> Transport AID - 10.1681/ASN.2014070658 DP - 2015 Nov 01 TA - Journal of the American Society of Nephrology PG - 2678--2690 VI - 26 IP - 11 4099 - http://jasn.asnjournals.org/content/26/11/2678.short 4100 - http://jasn.asnjournals.org/content/26/11/2678.full SO - J. Am. Soc. Nephrol.2015 Nov 01; 26 AB - 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 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+.