Protein Kinase G Inhibits Flow-Induced Ca2+ Entry into Collecting Duct Cells
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AbstractThe renal cortical collecting duct (CCD) contributes to the maintenance of K+ homeostasis by modulating renal K+ secretion. Cytosolic Ca2+ ([Ca2+](i)) mediates flow-induced K+ secretion in the CCD, but the mechanisms regulating flow-induced Ca2+ entry into renal epithelial cells are not well understood. Here, we found that atrial natriuretic peptide, nitric oxide, and cyclic guanosine monophosphate (cGMP) act through protein kinase G (PKG) to inhibit flow-induced increases in [Ca2+](i) in M1-CCD cells. Coimmuno-precipitation, double immunostaining, and functional studies identified heteromeric TRPV4-P2 channels as the mediators of flow-induced Ca2+ entry into M1-CCD cells and HEK293 cells that were coexpressed with both TRPV4 and TRPP2. In these HEK293 cells, introducing point mutations at two putative PKG phosphorylation sites on TRPP2 abolished the ability of cGMP to inhibit flow-induced Ca2+ entry. In addition, treating M1-CCD cells with fusion peptides that compete with the endogenous PKG phosphorylation sites on TRPP2 also abolished the cGMP-mediated inhibition of the flow-induced Ca2+ entry. Taken together, these data suggest that heteromeric TRPV4-P2 channels mediate the flow-induced entry of Ca2+ into collecting duct cells. Furthermore, substances such as atrial natriuretic peptide and nitric oxide, which increase cGMP, abrogate flow-induced Ca2+ entry through PKG-mediated inhibition of these channels.
All Author(s) ListDu J, Wong WY, Sun L, Huang Y, Yao XQ
Journal nameJournal of the American Society of Nephrology
Year2012
Month7
Day1
Volume Number23
Issue Number7
PublisherAmerican Society of Nephrology
Pages1172 - 1180
ISSN1046-6673
eISSN1533-3450
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesUrology & Nephrology; UROLOGY & NEPHROLOGY

Last updated on 2020-18-10 at 00:36