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Angiotensin II (AngII) diminishes the effect of SGK1 on WNK4‐mediated inhibition of ROMK1 channels
Author(s) -
Yue Peng,
Lin Daohong,
Pan Chunyang,
Sun Peng,
Wang Wenhui
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.610.2
Subject(s) - chemistry , sgk1 , angiotensin ii , phosphorylation , tyrosine , tyrosine kinase , medicine , patch clamp , endocrinology , microbiology and biotechnology , signal transduction , biology , biochemistry , receptor
We used the perforated whole‐cell patch‐clamp to examine the effect of AngII on ROMK1 channels in HEK293T cells transfected with GFP‐ROMK1. Application of AngII inhibited ROMK1 channels in a dose‐dependent manner. The inhibitory effect of AngII on ROMK1 was abolished by losartan (AT1R antagonist), GF109203x (PKC inhibitor) or siRNA of c‐Src. The notion that c‐Src was involved in mediating the effect of AngII on ROMK1 channels was also suggested by the finding that AngII stimulated the tyrosine phosphorylation of c‐Src on tyrosine residue 416 and increased the tyrosine phosphorylation of ROMK1 channels. AngII failed to inhibit K channels in cells transfected with ROMK1 mutant (R1Y337A) in which the tyrosine phosphorylation site was mutated. In contrast, expression of WNK4 was still able to inhibit R1Y337A and the inhibitory effect of WNK4 was abolished by SGK1. However, although AngII had no effect on R1Y337A regardless of SGK1 presence, AngII restored the WNK4‐induced inhibition of R1Y337A in the presence of SGK1. We conclude that AngII inhibited ROMK1 channels by two mechanisms: stimulating the tyrosine phosphorylation of ROMK channels and enhancing the WNK‐induced inhibition of ROMK1. Since volume‐depletion increased aldosterone and AngII level, AngII could play an important role in suppressing K secretion while stimulating Na absorption in aldosterone‐sensitive nephron.