Genetic evidence for functional role of ryanodine receptor 1 in pulmonary artery smooth muscle cells.
Genetic evidence for functional role of ryanodine receptor 1 in pulmonary artery smooth muscle cells.
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DOI：
10.1007/s00424-008-0556-8
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发表时间：
2009-02
影响因子：
4.5
通讯作者：
Wang, Yong-Xiao
中科院分区：
文献类型：
--
作者：
Li, Xiao-Qiang;Zheng, Yun-Min;Rathore, Rakesh;Ma, Jianjie;Takeshima, Hiroshi;Wang, Yong-Xiao
关键词：
众所周知，Ryanodine受体1（RyR 1）在全身和肺血管平滑肌细胞（SMC）中表达;然而，其功能作用在很大程度上仍然未知。在本研究中，我们试图确定RyR 1在膜去极化，神经递质和缺氧诱导的Ca 2+释放和收缩肺动脉平滑肌细胞（PASMCs）使用RyR 1纯合和杂合基因缺失（RyR 1-/-和RyR 1 +/-）小鼠的潜在重要性。我们的结果表明，胚胎RyR 1-/-和成人RyR+/-细胞中自发的局部Ca 2+释放和咖啡因诱导的整体Ca 2+释放显着减少。在正常Ca 2+或无Ca 2+的细胞外溶液中，RyR 1 −/−和RyR 1 +/− PASMCs在高K+下膜去极化后[Ca 2 +]i的增加显著减弱。类似地，在细胞外Ca 2+存在或不存在的情况下，RyR 1 +/−肺动脉中由膜去极化引起的肌肉收缩减少。神经递质受体激动剂和肌醇1，4，5-三磷酸在RyR 1 −/−和RyR 1 +/−细胞中引起的[Ca 2 +]i增加要小得多。我们还发现，神经递质诱发的肌肉收缩在RyR 1 +/−肺动脉中受到显著抑制。缺氧诱导的[Ca 2 +]i增加和收缩在RyR 1 −/−和/或RyR 1 +/− PASMCs中大部分被阻断。总的来说，我们的研究结果提供了遗传学证据的RyR 1在自发性局部Ca 2+释放，膜去极化，神经递质，以及缺氧诱导的全球Ca 2+释放和随之而来的收缩PASMCs的功能的重要性。
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.
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影响因子：
56.9
作者：
NELSON, MT;CHENG, H;LEDERER, WJ
通讯作者：
LEDERER, WJ
DOI：
10.1152/ajplung.00468.2001
发表时间：
2002-08-01
影响因子：
4.9
作者：
Remillard, CV;Zhang, WM;Sham, JSK
通讯作者：
Sham, JSK
影响因子：
7.3
作者：
Ng, L. C.;Wilson, S. M.;Hume, J. R.
通讯作者：
Hume, J. R.
影响因子：
64.8
作者：
TAKESHIMA, H;IINO, M;NODA, T
通讯作者：
NODA, T
DOI：
10.1152/ajpheart.00843.2001
发表时间：
2002-04-01
影响因子：
4.8
作者：
Tang, WX;Chen, YF;Li, PL
通讯作者：
Li, PL