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Single-channel Analysis and Calcium Imaging in the Podocytes of the Freshly Isolated Glomeruli
Published on: June 27, 2015
TRPC6 enhances angiotensin II-induced albuminuria
Jason Eckel1, Peter J Lavin, Elizabeth A Finch
1Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA.
Journal of the American Society of Nephrology : JASN
|January 25, 2011
Summary
TRPC6 channel deficiency protected mice from kidney damage and albuminuria during hypertension. TRPC6 blockade may offer a new therapy for proteinuric kidney disease.
Area of Science:
- Nephrology
- Molecular Biology
- Physiology
Background:
- Mutations in the canonical transient receptor potential cation channel 6 (TRPC6) cause familial focal segmental glomerulosclerosis (FSGS).
- The precise role of TRPC6 in kidney disease pathogenesis remains unclear.
- TRPC6-deficient mice were utilized to investigate TRPC6 function in the kidney.
Purpose of the Study:
- To elucidate the role of TRPC6 in the kidney.
- To determine if TRPC6 deficiency impacts susceptibility to hypertension and renal injury.
- To investigate the effect of TRPC6 on podocyte function.
Main Methods:
- TRPC6-deficient and wild-type mice were infused with angiotensin II for 28 days.
- Blood pressure and albumin excretion rates were monitored.
- Glomerular histomorphology was assessed using light and electron microscopy.
- Whole-cell patch-clamp recordings were performed on cultured podocytes.
Main Results:
- TRPC6-deficient mice exhibited significantly reduced albuminuria during angiotensin II infusion compared to wild-type mice.
- Hypertension levels were similar between groups.
- Angiotensin II and TRPC6 activator increased cell-membrane currents in wild-type podocytes, an effect abolished by TRPC6 deficiency.
- TRPC6 appears to mediate angiotensin II-induced calcium influx in podocytes.
Conclusions:
- TRPC6 channel activity promotes albuminuria, likely via angiotensin II-dependent calcium signaling in podocytes.
- TRPC6 deficiency confers protection against hypertension-induced kidney injury.
- TRPC6 blockade represents a potential therapeutic strategy for proteinuric kidney diseases.
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