Renal Ca2+ handling in sgk1 knockout mice.
Coexpression studies in Xenopus oocytes revealed the ability of the serum- and glucocorticoid-inducible kinase 1 (SGK1) to stimulate the renal epithelial Ca(2+) channel TRPV5. SGK1 increases the abundance of the channel protein in the plasma membrane, an effect requiring the participation of the Na(+)/H(+) exchanger regulating factor 2 (NHERF2). The present study was performed to explore the role of SGK1 in the regulation of renal Ca(2+) handling in vivo. To this end, TRPV5, calbindin D-28K abundance, and renal Ca(2+) excretion were analyzed in gene-targeted mice lacking functional SGK1 (sgk1( -/- )) and their age- and sex-matched littermates (sgk1( +/+ )). Immunohistochemistry revealed lower abundance of TRPV5 and calbindin D-28K protein in sgk1( -/- ) mice than in sgk1( +/+ ) mice, both fed with control diet. Feeding the mice a Ca(2+)-deficient diet marked ly increased TRPV5 protein abundance in both genotypes. Renal Ca(2+) excretion under control diet was significantly lower in sgk1 ( -/- ) than in sgk1( +/+ ) mice. The Ca(2+)-deficient diet decreased renal excretion of Ca(2+) to the same levels in both phenotypes. Furosemide increased fractional Ca(2+) excretion and dissipated the difference between phenotypes. We conclude that lack of SGK1 may lead to decrease in TRPV5 abundance in connecting tubules but does not abrogate TRPV5 regulation. The decrease in abundance of TRPV5 in connecting tubules of sgk1( -/- ) mice is presumably compensated for by enhanced Ca(2+) reabsorption in upstream nephron segments such as the loop of Henle, which may indirectly result from impaired SGK1-dependent Na(+) reabsorption in the aldosterone-sensitive distal part of the nephron, salt loss, and enhanced Na(+) (and Ca(2+)) reabsorption in those upstream nephron segments.
Sandulache
Diana
D
Department of Physiology, University of Tübingen, Gmelinstrasse 5, 72076 Tübingen, Germany.
Grahammer
Florian
F
Artunc
Ferruh
F
Henke
Guido
G
Hussain
Azeemudeen
A
Nasir
Omaima
O
Mack
Andreas
A
Friedrich
Björn
B
Vallon
Volker
V
Wulff
Peer
P
Kuhl
Dietmar
D
Palmada
Monica
M
Lang
Florian
F