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Updated: Jun 5, 2026
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.
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 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.
Insights
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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