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Caveolin-1 Deficiency Inhibits the Basolateral K+ Channels in the Distal
Convoluted Tubule and Impairs Renal K+ and Mg2+ Transport
#MMPMID25848073
Wang L
; Zhang C
; Su X
; Lin DH
; Wang W
J Am Soc Nephrol
2015[Nov]; 26
(11
): 2678-90
PMID25848073
show ga
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-?. 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(+).
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