Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text PDF (Full Text) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JGP Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zheng, Y.-M. Articles by Wang, Y.-X. Search for Related Content PubMed PubMed Citation Articles by Zheng, Y.-M. Articles by Wang, Y.-X. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB CAFFEINE CALCIUM COMPOUNDS CALCIUM, ELEMENTAL Social Bookmarking                      What's this?

¹ Center for Cardiovascular Sciences, Neuroscience, and Neuropharmacology, Albany Medical College, Albany, NY 12208
² Molecular Medicine Section, Department of Neuroscience, University of Siena, Siena, Italy 53100
³ Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853

Correspondence to Yong-Xiao Wang: wangy{at}mail.amc.edu

In this study we examined the expression of RyR subtypes and the role of RyRs in neurotransmitter- and hypoxia-induced Ca²⁺ release and contraction in pulmonary artery smooth muscle cells (PASMCs). Under perforated patch clamp conditions, maximal activation of RyRs with caffeine or inositol triphosphate receptors (IP₃Rs) with noradrenaline induced equivalent increases in [Ca²⁺]_i and Ca²⁺-activated Cl^– currents in freshly isolated rat PASMCs. Following maximal IP₃-induced Ca²⁺ release, neither caffeine nor chloro-m-cresol induced a response, whereas prior application of caffeine or chloro-m-cresol blocked IP₃-induced Ca²⁺ release. In cultured human PASMCs, which lack functional expression of RyRs, caffeine failed to affect ATP-induced increases in [Ca²⁺]_i in the presence and absence of extracellular Ca²⁺. The RyR antagonists ruthenium red, ryanodine, tetracaine, and dantrolene greatly inhibited submaximal noradrenaline– and hypoxia-induced Ca²⁺ release and contraction in freshly isolated rat PASMCs, but did not affect ATP-induced Ca²⁺ release in cultured human PASMCs. Real-time quantitative RT-PCR and immunofluorescence staining indicated similar expression of all three RyR subtypes (RyR1, RyR2, and RyR3) in freshly isolated rat PASMCs. In freshly isolated PASMCs from RyR3 knockout (RyR3^–/–) mice, hypoxia-induced, but not submaximal noradrenaline–induced, Ca²⁺ release and contraction were significantly reduced. Ruthenium red and tetracaine can further inhibit hypoxic increase in [Ca²⁺]_i in RyR3^–/– mouse PASMCs. Collectively, our data suggest that (a) RyRs play an important role in submaximal noradrenaline– and hypoxia-induced Ca²⁺ release and contraction; (b) all three subtype RyRs are expressed; and (c) RyR3 gene knockout significantly inhibits hypoxia-, but not submaximal noradrenaline–induced Ca²⁺ and contractile responses in PASMCs.

Key Words: ryanodine receptor • inositol triphosphate receptor • hypoxia • neurotransmitter • pulmonary artery smooth muscle cell

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. C. Ng, B. D. Kyle, A. R. Lennox, X.-M. Shen, W. J. Hatton, and J. R. Hume Cell culture alters Ca2+ entry pathways activated by store-depletion or hypoxia in canine pulmonary arterial smooth muscle cells Am J Physiol Cell Physiol, January 1, 2008; 294(1): C313 - C323. [Abstract] [Full Text] [PDF]

				O. Ostrovskaya, R. Goyal, N. Osman, C. E. McAllister, I. N. Pessah, J. R. Hume, and S. M. Wilson Inhibition of Ryanodine Receptors by 4-(2-Aminopropyl)-3,5-dichloro-N,N-dimethylaniline (FLA 365) in Canine Pulmonary Arterial Smooth Muscle Cells J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 381 - 390. [Abstract] [Full Text] [PDF]

				D. Parthimos, R. E. Haddock, C. E. Hill, and T. M. Griffith Dynamics of A Three-Variable Nonlinear Model of Vasomotion: Comparison of Theory and Experiment Biophys. J., September 1, 2007; 93(5): 1534 - 1556. [Abstract] [Full Text] [PDF]

				J. Wang, L. Weigand, J. Foxson, L. A. Shimoda, and J. T. Sylvester Ca2+ signaling in hypoxic pulmonary vasoconstriction: effects of myosin light chain and Rho kinase antagonists Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L674 - L685. [Abstract] [Full Text] [PDF]

				S. Pouvreau, L. Royer, J. Yi, G. Brum, G. Meissner, E. Rios, and J. Zhou Ca2+ sparks operated by membrane depolarization require isoform 3 ryanodine receptor channels in skeletal muscle PNAS, March 20, 2007; 104(12): 5235 - 5240. [Abstract] [Full Text] [PDF]

				W. Du, T. J. McMahon, Z.-S. Zhang, J. A. Stiber, G. Meissner, and J. P. Eu Excitation-Contraction Coupling in Airway Smooth Muscle J. Biol. Chem., October 6, 2006; 281(40): 30143 - 30151. [Abstract] [Full Text] [PDF]

				D. MacMillan, S. Chalmers, T. C. Muir, and J. G. McCarron IP3-mediated Ca2+ increases do not involve the ryanodine receptor, but ryanodine receptor antagonists reduce IP3-mediated Ca2+ increases in guinea-pig colonic smooth muscle cells J. Physiol., December 1, 2005; 569(2): 533 - 544. [Abstract] [Full Text] [PDF]

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents