NDLI: Genetic evidence for functional role of ryanodine receptor 1 in pulmonary artery smooth muscle cells

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Genetic evidence for functional role of ryanodine receptor 1 in pulmonary artery smooth muscle cells

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Li, Xiao-Qiang Zheng, Yun-Min Rathore, Rakesh Ma, Jianjie Takeshima, Hiroshi Wang, Yong-Xiao
Description	Country affiliation: United States Author Affiliation: Li XQ ( Center for Cardiovascular Sciences (MC-8), Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA.)
Abstract	Ryanodine receptor 1 (RyR1) is well-known to be expressed in systemic and pulmonary vascular smooth muscle cells (SMCs); however, its functional roles remain largely unknown. In the present study, we attempted to determine the potential importance of RyR1 in membrane depolarization-, neurotransmitter-, and hypoxia-induced Ca2+ release and contraction in pulmonary artery SMCs (PASMCs) using RyR1 homozygous and heterozygous gene deletion (RyR1-/- and RyR1+/-) mice. Our results indicate that spontaneous local Ca2+ release and caffeine-induced global Ca2+ release are significantly reduced in embryonic RyR1-/- and adult RyR+/- cells. An increase in [Ca2+]i following membrane depolarization with high K+ is markedly attenuated in RyR1-/- and RyR1+/- PASMCs in normal Ca2+ or Ca2+-free extracellular solution. Similarly, muscle contraction evoked by membrane depolarization is reduced in RyR1+/- pulmonary arteries in the presence or absence of extracellular Ca2+. Neurotransmitter receptor agonists and inositol 1,4,5-triphosphate elicit a much smaller increase in [Ca2+]i in both RyR1-/- and RyR1+/- cells. We have also found that neurotransmitter-evoked muscle contraction is significantly inhibited in RyR1+/- pulmonary arteries. Hypoxia-induced increase in [Ca2+]i and contraction are largely blocked in RyR1-/- and/or RyR1+/- PASMCs. Collectively, our findings provide genetic evidence for the functional importance of RyR1 in spontaneous local Ca2+ release, and membrane depolarization-, neurotransmitter-, as well as hypoxia-induced global Ca2+ release and attendant contraction in PASMCs.
File Format	HTM / HTML
ISSN	00316768
e-ISSN	14322013
DOI	10.1007/s00424-008-0556-8
Journal	Pflügers Archiv - European Journal of Physiology
Issue Number	4
Volume Number	457
Language	English
Publisher	Springer
Publisher Date	2009-02-01
Publisher Place	Germany
Access Restriction	Open
Subject Keyword	Discipline Physiology Calcium Signaling Physiology Myocytes, Smooth Muscle Pulmonary Artery Cytology Ryanodine Receptor Calcium Release Channel Animals Caffeine Metabolism Calcium Anoxia Membrane Potentials Mice Mice, Knockout Muscle Contraction Neurotransmitter Agents Patch-clamp Techniques Pregnancy Genetics Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical) Clinical Biochemistry

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