Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation
Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation
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DOI：
10.1126/science.279.5348.234
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发表时间：
1998-01-09
期刊：
影响因子：
56.9
通讯作者：
Stamler, JS
中科院分区：
文献类型：
--
作者：
Xu, L;Eu, JP;Stamler, JS
据报道，几种离子通道是氧化还原反应性的，但活性变化的分子基础尚不清楚。本文探讨了一氧化氮对犬心肌钙释放通道（兰尼碱受体）的作用机制。该四聚体通道含有类似于84个游离巯基，并且在体内被S-亚硝基化。多达12个位点（每个CRC亚基3个）的S-亚硝基化导致进行性通道激活，该激活被脱亚硝基化逆转。相比之下，每个CRC氧化20至24个硫醇（每个亚基5或6个）对通道功能没有影响。另外的硫醇（或另一类硫醇）的氧化产生不可逆的活化。因此，CRC似乎受到多S-亚硝基化（多共价连接）的调节，而氧化可导致失控。这些结果表明，离子通道可以区分亚硝化和氧化信号，并表明：CRC是由翻译后化学修饰的硫。
Several ion channels are reportedly redox responsive, but the molecular basis for the changes in activity is not known. The mechanism of nitric oxide action on the cardiac calcium release channel (ryanodine receptor) (CRC) in canines was explored. This tetrameric channel contains similar to 84 free thiols and is S-nitrosylated in vivo. S-Nitrosylation of up to 12 sites (3 per CRC subunit) led to progressive channel activation that was reversed by denitrosylation. In contrast, oxidation of 20 to 24 thiols per CRC (5 or 6 per subunit) had no effect on channel function. Oxidation of additional thiols (or of another class of thiols) produced irreversible activation. The CRC thus appears to be regulated by poly-S-nitrosylation (multiple covalent attachments), whereas oxidation can lead to loss of control. These results reveal that ion channels can differentiate nitrosative from oxidative signals and indicate that: the CRC is regulated by posttranslational chemical modification(s) of sulfurs.