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Store‐operated Ca2+ entry (SOCE) and canonical transient receptor potential channel (TRPC) proteins are expressed in rat distal pulmonary venous smooth muscle
Author(s) -
Peng Gongyong,
Lu Wenju,
Shimoda Larissa,
Ran Pixin,
Sylvester J,
Wang Jian
Publication year - 2009
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.23.1_supplement.999.11
Subject(s) - trpc , transient receptor potential channel , trpc1 , trpc3 , cyclopiazonic acid , trpc5 , extracellular , hypoxic pulmonary vasoconstriction , vascular smooth muscle , trpc6 , chemistry , voltage dependent calcium channel , medicine , hypoxia (environmental) , trpv , endocrinology , nifedipine , intracellular , microbiology and biotechnology , pulmonary hypertension , calcium , receptor , biology , biochemistry , smooth muscle , trpv1 , organic chemistry , oxygen
Chronic hypoxia causes remodeling and alters contractile responses in both pulmonary arteries (PA) and pulmonary veins (PV). Although PA have been studied extensively in this disorder, the mechanisms by which PV respond to hypoxia and whether these responses contribute to chronic hypoxic pulmonary hypertension (CHPH) remain poorly understood. In pulmonary arterial smooth muscle, we have previously demonstrated that influx of Ca 2+ through store‐operated calcium channels (SOCC) thought to be composed of TRPC proteins is likely to play an important role in development of CHPH. To determine whether this mechanism could also be operative in pulmonary venous smooth muscle, we measured intracellular Ca 2+ concentration ([Ca 2+ ] i ) by fura‐2 fluorescence microscopy in primary cultures of pulmonary venous smooth muscle cells (PVSMC) isolated from rat distal PV. In cells perfused with Ca 2+ ‐free media containing cyclopiazonic acid (10 µM) and nifedipine (5 µM) to deplete SR Ca 2+ stores and block voltage‐dependent Ca 2+ channels, restoration of extracellular Ca 2+ caused marked increases in [Ca 2+ ] i whereas MnCl 2 (200 µM) quenched fura‐2 fluorescence, indicating SOCE. SKF‐96365 and NiCl 2 , antagonists of SOCC, blocked SOCE at concentrations that did not alter Ca 2+ responses to 60 mM KCl. Real‐time PCR revealed mRNA expression of TRPC1, ‐4, and ‐6, and Western blotting confirmed protein expression of TRPC1, ‐4, and ‐6 in both rat de‐endolthelialized distal PV and PVSMC. Our results suggest that SOCE through Ca 2+ channels composed of TRPC proteins could contribute to Ca 2+ signaling in distal PVSMC.