期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 27, 页码 11418-11423出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0813307106
关键词
muscarinic receptors; ryanodine receptors
资金
- National Institutes of Health (NIH) [R01HL071000]
- NIH Intramural Research Program
- American Lung Association Research [19994]
- American Heart Association (AHA) Scientist Development [0630236N, 0730242N]
- AHA Established Investigator Award [0340160N]
Membrane depolarization activates voltage-dependent Ca2+ channels (VDCCs) inducing Ca2+ release via ryanodine receptors (RyRs), which is obligatory for skeletal and cardiac muscle contraction and other physiological responses. However, depolarization-induced Ca2+ release and its functional importance as well as underlying signaling mechanisms in smooth muscle cells (SMCs) are largely unknown. Here we report that membrane depolarization can induce RyR-mediated local Ca2+ release, leading to a significant increase in the activity of Ca2+ sparks and contraction in airway SMCs. The increased Ca2+ sparks are independent of VDCCs and the associated extracellular Ca2+ influx. This format of local Ca2+ release results from a direct activation of G protein-coupled, M-3 muscarinic receptors in the absence of exogenous agonists, which causes activation of Gq proteins and phospholipase C, and generation of inositol 1,4,5-triphosphate (IP3), inducing initial Ca2+ release through IP3 receptors and then further Ca2+ release via RyR2 due to a local Ca2+-induced Ca2+ release process. These findings demonstrate an important mechanism for Ca2+ signaling and attendant physiological function in SMCs.
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