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Ca 2+ ‐activated Cl − channels contribute to regulating store‐ and receptor‐operated Ca 2+ entry in human pulmonary arterial smooth muscle cells
Author(s) -
Yamamura Aya,
Yamamura Hisao,
Yuan Jason X.J.
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.lb506
Subject(s) - niflumic acid , cyclopiazonic acid , chemistry , cytosol , transient receptor potential channel , dids , intracellular , biophysics , biochemistry , receptor , biology , membrane , enzyme
Cytosolic Ca 2+ ([Ca 2+ ] cyt ) plays a fundamental role in regulating cell functions in pulmonary arterial smooth muscle cells (PASMC). A rise in [Ca 2+ ] cyt triggers pulmonary vasoconstriction and stimulates PASMC proliferation. [Ca 2+ ] cyt is mainly increased by Ca 2+ release from intracellular stores and Ca 2+ influx through plasmalemmal Ca 2+ ‐permeable channels. Given the high concentration of intracellular Cl − in PASMC, Ca 2+ ‐activated Cl − (Cl Ca ) channels play an important role in regulating membrane potential and cell excitability of PASMC. In this study, we examined whether Cl Ca channels were involved in regulating [Ca 2+ ] cyt in PASMC via store‐operated (SOCE) and receptor‐operated (ROCE) Ca 2+ entry. [Ca 2+ ] cyt was measured in human PASMCs loaded with fura‐2/AM using a Nikon digital fluorescence imaging system. SOCE was induced by passive depletion of Ca 2+ from the sarcoplasmic reticulum (SR) by cyclopiazonic acid (10 μM). Inhibition of Cl Ca channels by 100 μM niflumic acid significantly reduced both transient and plateau phases of SOCE. In addition, angiotensin II‐mediated increase in [Ca 2+ ] cyt via ROCE was markedly attenuated by the Cl Ca channel inhibitors, niflumic acid, flufenamic acid or DIDS. These results suggest that function of Cl Ca channels contributes to regulating [Ca 2+ ] cyt by affecting SOCE and ROCE in human PASMC. Research Funding Source: NIH grants (HL066012 and HL 098053).