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Hydrogen Peroxide Activates Calcium Entry in Cultured Human Podocytes
Author(s) -
Wang Ning,
Wang LiHua,
Stewart Ver L,
Zhou Yiqun,
Ma HePing
Publication year - 2011
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.25.1_supplement.1041.46
Subject(s) - trpc6 , chemistry , reactive oxygen species , channel blocker , hydrogen peroxide , biophysics , oxidative stress , microbiology and biotechnology , podocyte , intracellular , patch clamp , calcium , biochemistry , receptor , endocrinology , transient receptor potential channel , biology , kidney , organic chemistry , proteinuria
Several lines of evidence suggest that oxidative stress results in podocyte injury. However, the underlying mechanism remains largely unknown. In the present study, we used confocal microscopy and patch‐clamp techniques to investigate how reactive oxygen species (ROS) regulate intracellular Ca 2+ concentration [Ca 2+ ] i in cultured human podocytes. Ca 2+ imaging experiments showed that hydrogen peroxide, one of ROS, strongly elevated [Ca 2+ ] i . The elevation was dependent on extracellular Ca 2+ and was abolished both by SKF‐96365, a Ca 2+ ‐permeable channel blocker, and by tetraethylammonium, a K + channel blocker. Cell‐attached experiments showed that hydrogen peroxide stimulated both a TRPC6‐like channel and Ca 2+ ‐activated K + channels in podocytes. Since it has been shown that TRPC6 acts as a Ca 2+ ‐permeable channel only when the membrane is hyperpolarized, K + channels may play a permissive role in allowing TRPC6 to be permeable to Ca 2+ . These data suggest that oxidative stress may activate a positive feedback loop formed between TRPC6 and Ca 2+ ‐activated K + channels to cause podocyte injury via a massive elevation of [Ca 2+ ] i . This work is supported by NIH Grant 2R01‐DK‐067110 to H.P.M.