TRPC6 enhances angiotensin II-induced albuminuria

Jason Eckel, Peter J. Lavin, Elizabeth A. Finch, Nirvan Mukerji, Jarrett Burch, Rasheed Gbadegesin, Guanghong Wu, Brandy Bowling, Alison Byrd, Gentzon Hall, Matthew Sparks, Zhu Shan Zhang, Alison Homstad, Laura Barisoni, Lutz Birbaumer, Paul Rosenberg, Michelle P. Winn

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Mutations in the canonical transient receptor potential cation channel 6 (TRPC6) are responsible for familial forms of adult onset focal segmental glomerulosclerosis (FSGS). The mechanisms by which TRPC6 mutations cause kidney disease are not well understood. We used TRPC6-deficient mice to examine the function of TRPC6 in the kidney. We found that adult TRPC6-deficient mice had BP and albumin excretion rates similar to wild-type animals. Glomerular histomorphology revealed no abnormalities on both light and electron microscopy. To determine whether the absence of TRPC6 would alter susceptibility to hypertension and renal injury, we infused mice with angiotensin II continuously for 28 days. Although both groups developed similar levels of hypertension, TRPC6-deficient mice had significantly less albuminuria, especially during the early phase of the infusion; this suggested that TRPC6 adversely influences the glomerular filter. We used whole-cell patch-clamp recording to measure cellmembrane currents in primary cultures of podocytes from both wild-type and TRPC6-deficient mice. In podocytes from wild-type mice, angiotensin II and a direct activator of TRPC6 both augmented cell-membrane currents; TRPC6 deficiency abrogated these increases in current magnitude. Our findings suggest that TRPC6 promotes albuminuria, perhaps by promoting angiotensin II-dependent increases in Ca2+, suggesting that TRPC6 blockade may be therapeutically beneficial in proteinuric kidney disease.

Original languageEnglish (US)
Pages (from-to)526-535
Number of pages10
JournalJournal of the American Society of Nephrology
Volume22
Issue number3
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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    Eckel, J., Lavin, P. J., Finch, E. A., Mukerji, N., Burch, J., Gbadegesin, R., Wu, G., Bowling, B., Byrd, A., Hall, G., Sparks, M., Zhang, Z. S., Homstad, A., Barisoni, L., Birbaumer, L., Rosenberg, P., & Winn, M. P. (2011). TRPC6 enhances angiotensin II-induced albuminuria. Journal of the American Society of Nephrology, 22(3), 526-535. https://doi.org/10.1681/ASN.2010050522