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Function of TRPC1/TRPC4 complex in mesangial cells
Author(s) -
Sours Sherry,
Oberdorfer Joseph,
Ding Min,
Du Juan,
Ma Rong
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a767
Subject(s) - trpc , trpc1 , transient receptor potential channel , microbiology and biotechnology , immunocytochemistry , chemistry , trpc5 , endocrinology , biology , receptor , biochemistry
Store‐operated Ca 2+ channel (SOC) in glomerular mesangial cells (MCs) mediates Ca 2+ entry in response to circulating or locally produced vasoactive peptides. Recent evidence suggests that members of the canonical transient receptor potential (TRPC) protein family may constitute SOC. However, expression of TRPC subtypes and formation of TRPC heteromultimeric complexes appear to be cell‐type specific. Our laboratory has recently characterized TRPC expression in human MCs (HMCs), which includes TRPC1, 3, 4, and 6 at detectable protein levels. In the present study, we show that TRPC1 associates with TRPC4 by co‐immunoprecipitation and by fluorescent immunocytochemistry. RNA interference (RNAi) of TRPC1 expression, or inclusion of a TRPC1‐specific antibody in the patch pipette significantly depressed thapsigargin (TG) ‐induced Ca 2+ currents as measured by patch clamp. Accordingly, fluorescent ratiometry showed that over‐expression of TRPC1 enhanced TG‐induced capacitative Ca 2+ entry, while RNAi blockade of TRPC1 reduced this response. RNAi blockade of TRPC4 had a similar effect on TG‐induced Ca 2+ entry as TRPC1, while concurrent RNAi of TRPC1 and TRPC4 also had a comparable effect. Furthermore, TRPC1 knock‐down reduced HMC proliferation and contraction. These data suggest that TRPC1 and TRPC4 form a functional complex to mediate store‐operated Ca 2+ entry in HMCs. (Supported by AHA, SDG and NKF).