TRPC6 enhances angiotensin II-induced albuminuria.

Published

Journal Article

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 cell-membrane 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 Ca(2+), suggesting that TRPC6 blockade may be therapeutically beneficial in proteinuric kidney disease.

Full Text

Duke Authors

Cited Authors

  • Eckel, J; Lavin, PJ; Finch, EA; Mukerji, N; Burch, J; Gbadegesin, R; Wu, G; Bowling, B; Byrd, A; Hall, G; Sparks, M; Zhang, ZS; Homstad, A; Barisoni, L; Birbaumer, L; Rosenberg, P; Winn, MP

Published Date

  • March 2011

Published In

Volume / Issue

  • 22 / 3

Start / End Page

  • 526 - 535

PubMed ID

  • 21258036

Pubmed Central ID

  • 21258036

Electronic International Standard Serial Number (EISSN)

  • 1533-3450

Digital Object Identifier (DOI)

  • 10.1681/ASN.2010050522

Language

  • eng

Conference Location

  • United States