cADP ribose and [Ca(2+)](i) regulation in rat cardiac myocytes.
cADP ribose and [Ca(2+)](i) regulation in rat cardiac myocytes.
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DOI：
10.1152/ajpheart.2000.279.4.h1482
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发表时间：
2000-10
期刊：
影响因子：
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通讯作者：
Y. Prakash;Mathur S. Kannan;T. Walseth;Gary C. Sieck
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作者：
Y. Prakash;Mathur S. Kannan;T. Walseth;Gary C. Sieck
用实时共聚焦显微镜观察了cADP核糖（cADPR）诱导的急性分离的成年大鼠心室肌细胞内Ca（2+）浓度（[Ca（2+）]（i））反应。在静止的单个心肌细胞中，注射cADPR（0.1-10 μ M）诱导持续的浓度依赖性[Ca（2+）]（i）反应，范围为50至500 nM，可被20 μ M 8-氨基-cADPR（cADPR受体的特异性阻断剂）完全抑制。在显示自发[Ca（2+）]（i）波的心肌细胞中，增加cADPR浓度可使波频率增加至对照组的约250%。在电起搏心肌细胞（0.5 Hz，5 ms持续时间）中，cADPR以浓度依赖性方式增加[Ca（2+）]（i）瞬变的幅度，高达对照的150%。给予8-amino-cADPR可抑制自发波以及对电刺激的[Ca（2+）]（i）反应，即使在不存在外源性cADPR的情况下也是如此。然而，随后对5 mM咖啡因的[Ca（2+）]（i）反应仅被8-amino-cADPR部分抑制。相反，即使在ryanodine受体（RyR）通道被ryanodine阻断的条件下，高浓度的cADPR仍然诱导[Ca（2+）]（i）反应。这些结果表明，在心肌细胞中，cADPR通过RyR通道和不依赖于RyR通道的机制诱导肌浆网Ca（2+）释放。
cADP ribose (cADPR)-induced intracellular Ca(2+) concentration ([Ca(2+)](i)) responses were assessed in acutely dissociated adult rat ventricular myocytes using real-time confocal microscopy. In quiescent single myocytes, injection of cADPR (0.1-10 microM) induced sustained, concentration-dependent [Ca(2+)](i) responses ranging from 50 to 500 nM, which were completely inhibited by 20 microM 8-amino-cADPR, a specific blocker of the cADPR receptor. In myocytes displaying spontaneous [Ca(2+)](i) waves, increasing concentrations of cADPR increased wave frequency up to approximately 250% of control. In electrically paced myocytes (0.5 Hz, 5-ms duration), cADPR increased the amplitude of [Ca(2+)](i) transients in a concentration-dependent fashion, up to 150% of control. Administration of 8-amino-cADPR inhibited both spontaneous waves as well as [Ca(2+)](i) responses to electrical stimulation, even in the absence of exogenous cADPR. However, subsequent [Ca(2+)](i) responses to 5 mM caffeine were only partially inhibited by 8-amino-cADPR. In contrast, even under conditions where ryanodine receptor (RyR) channels were blocked with ryanodine, high cADPR concentrations still induced an [Ca(2+)](i) response. These results indicate that in cardiac myocytes, cADPR induces Ca(2+) release from the sarcoplasmic reticulum through both RyR channels and via mechanisms independent of RyR channels.