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Store-operated channels mediate ca2+ influx and contraction in rat pulmonary artery

Ng, L.C. and Gurney, A.M. (2001) Store-operated channels mediate ca2+ influx and contraction in rat pulmonary artery. Circulation Research, 89 (10). pp. 923-929. ISSN 0009-7330

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Cation channels activated by Ca2+ store depletion have been proposed to mediate Ca2+ influx in vascular smooth muscle cells. The aim of this study was to determine if store-operated channels have a functional role in pulmonary artery smooth muscle cells (PASMCs). In intact rat pulmonary artery rings, cyclopiazonic acid (CPA) produced a sustained contraction that was resistant to inhibition by nifedipine, but abolished in Ca2+-free solution and 50% blocked in the presence of 6 µmol/L Cd2+, 10 µmol/L Ni2+, 600 µmol/L La3+, and 7 µmol/L SKF96365. In freshly isolated PASMCs loaded with fura-2, CPA increased the intracellular Ca2+ concentration by stimulating dihydropyridine-resistant Ca2+ influx, which was 50% blocked by 10 µmol/L Ni2+ and 7 µmol/L SKF96365. In perforated-patch recordings, CPA activated a sustained inward current at negative membrane potentials, which persisted in cells dialyzed with BAPTA, showed a near linear dependence on membrane potential when Cs+ was the main intracellular cation, and was blocked by Ni2+, Cd2+, and SKF96365 at concentrations preventing contraction. The current showed a bimodal dependence on extracellular Ca2+, being enhanced 2-fold in the absence of Ca2+ and around 10-fold on reducing Ca from 1.8 to 0.2 mmol/L. RT-PCR revealed the expression of Trp1, Trp3, Trp4, Trp5, and Trp6 mRNA, whereas immunostaining identified Trp1, Trp3, Trp4, and Trp6 channel proteins in isolated PASMCs. At least one of these subunits may contribute to cation channels in PASMCs, which are activated by store depletion to bring about Ca2+ influx and contraction.

Item type: Article
ID code: 23645
Notes: Meeting abstract published in: The Journal of Physiology (2001), volume 536.
Keywords: store-operated channel, capacitative calcium entry, pulmonary artery smooth muscle, cation channel, Trp channel, Probabilities. Mathematical statistics, Physiology, Cardiology and Cardiovascular Medicine
Subjects: Science > Mathematics > Probabilities. Mathematical statistics
Department: Faculty of Engineering > Naval Architecture and Marine Engineering
Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences > Physiology and Pharmacology
Depositing user: Strathprints Administrator
Date Deposited: 06 Jul 2010 10:24
Last modified: 10 Dec 2015 19:14

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