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TRPC1 and STIM1 Mediate Capacitative Calcium Entry in Mouse Pulmonary Arterial Smooth Muscle Cells
Author(s) -
Ng Lih Chyuan,
McCormack Mary D.,
Shen XiaoMing,
Hume Joseph R.
Publication year - 2008
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.22.1_supplement.965.23
Subject(s) - trpc1 , nifedipine , stim1 , extracellular , western blot , transient receptor potential channel , trpc3 , voltage dependent calcium channel , chemistry , trpc , microbiology and biotechnology , calcium , endocrinology , medicine , biology , biochemistry , receptor , gene
Previous studies in pulmonary arterial smooth muscle cells (PASMCs) showed that TRPC1 channel mediates capacitative Ca 2+ entry (CCE) but the molecular signal(s) that activate TRPC1 in PASMCs remains unknown. The aim of the present study was to determine if TRPC1 mediate CCE through activation of STIM1 protein in mouse PASMCs. In primary cultured PASMCs loaded with fura‐2, 10μM CPA caused a rise in [Ca 2+ ] i but it was abolished when extracellular Ca 2+ was removed. Subsequent addition of 2mM Ca 2+ elicited a transient rise in [Ca 2+ ] i that was partially inhibited by 10μM nifedipine, leaving a nifedipine‐insensitive transient and nifedipine‐insensitive sustained rise in [Ca 2+ ] i . The nifedipine‐insensitive sustained, but not transient rise in [Ca 2+ ] i was inhibited in cells pretreated with antibodies raised against extracellular epitope of TRPC1 and STIM1. RT‐PCR revealed TRPC1 and STIM1 mRNAs, whereas Western blot analysis identified TRPC1 and STIM1 proteins in cultured mouse PASMCs. Taken together, store‐depletion causes activation of voltage‐operated Ca 2+ entry, CCE and another as yet unidentified voltage‐independent Ca 2+ entry pathway. These data suggest that CCE is mediated by TRPC1 channel possibly through activation of STIM1 protein in mouse PASMCs. (Supported by HL49254 and NCRR P20RR15581)