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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Membrane depolarization causes a direct activation of G protein-coupled receptors leading to local Ca~(2+) release in smooth muscle
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Membrane depolarization causes a direct activation of G protein-coupled receptors leading to local Ca~(2+) release in smooth muscle

机译:膜去极化导致G蛋白偶联受体的直接激活,导致平滑肌中局部Ca〜(2+)释放

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摘要

Membrane depolarization activates voltage-dependent Ca~(2+) channels (VDCCs) inducing Ca~(2+) release via ryanodine receptors (RyRs), which is obligatory for skeletal and cardiac muscle contraction and other physiological responses. However, depolarization-induced Ca~(2+) 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 Ca~(2+) release, leading to a significant increase in the activity of Ca~(2+) sparks and contraction in airway SMCs. The increased Ca~(2+) sparks are independent of VDCCs and the associated extracellular Ca~(2+) influx. This format of local Ca~(2+) 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 Ca~(2+) release through IP3 receptors and then further Ca~(2+) release via RyR2 due to a local Ca~(2+)-induced Ca~(2+) release process. These findings demonstrate an important mechanism for Ca~(2+) signaling and attendant physiological function in SMCs.
机译:膜去极化激活了依赖电压的Ca〜(2+)通道(VDCCs),通过ryanodine受体(RyRs)诱导Ca〜(2+)释放,这对于骨骼肌和心肌的收缩以及其他生理反应是必不可少的。然而,去极化诱导的Ca〜(2+)释放及其功能重要性以及在平滑肌细胞(SMC)中的潜在信号传导机制尚不清楚。在这里,我们报道膜去极化可以诱导RyR介导的局部Ca〜(2+)释放,从而导致Ca〜(2+)火花的活性显着增加以及气道SMC的收缩。增加的Ca〜(2+)火花与VDCC和相关的细胞外Ca〜(2+)流入无关。这种形式的Ca〜(2+)局部释放是由于在没有外源激动剂的情况下直接激活G蛋白偶联的M_3毒蕈碱受体而引起的,从而引起Gq蛋白和磷脂酶C的激活以及肌醇1,4, 5-三磷酸(IP3),通过IP3受体诱导最初的Ca〜(2+)释放,然后由于局部Ca〜(2+)诱导的Ca〜(2+)释放,进一步通过RyR2释放Ca〜(2+)。处理。这些发现证明了SMC中Ca〜(2+)信号传导和伴随的生理功能的重要机制。

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  • 作者单位

    Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208;

    Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208;

    Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208;

    Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208;

    Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208;

    Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892;

    Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    muscarinic receptors; ryanodine receptors;

    机译:毒蕈碱受体;ryanodine受体;

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