Eu J P, Xu L, Stamler J S, Meissner G
Howard Hughes Medical Institute, Department of Medicine, Divisions of Pulmonary and Cardiovascular Medicine, and Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Biochem Pharmacol. 1999 May 15;57(10):1079-84. doi: 10.1016/s0006-2952(98)00360-8.
The ryanodine receptors (RyRs) are large intracellular calcium release channels that play an important role in the control of the calcium levels in excitable and non-excitable cells. Many endogenous modulators such as Mg2+, ATP, or calmodulin can affect the channel activities of the three known mammalian RyR isoforms. RyRs also are known to be redox-responsive. However, the molecular basis and the physiological relevance of redox modulation of RyRs are unclear. Recent evidence suggests that nitric oxide (NO) and related molecules may be endogenous regulators of the skeletal and cardiac muscle RyRs. The two tissues express nitric oxide synthases (NOSs), and NO or NO-related species have been shown to affect Ca2+ release channel activities directly via covalent modifications of thiol groups. Both an oxidative and a nitrosative modification of RyRs have been described, leading to either a reversible or irreversible alteration of RyR ion channel activity. Additional mechanisms of regulation may include cyclic GMP-dependent signaling pathways and NO modification of RyR regulatory proteins such as the surface membrane L-type Ca2+ channel. Modification of RyRs by NO may influence a variety of physiological functions such as insulin release, vasomotor control, and muscle contraction.
兰尼碱受体（RyRs）是大型细胞内钙释放通道，在可兴奋细胞和非可兴奋细胞的钙水平控制中发挥重要作用。许多内源性调节剂，如Mg2+、ATP或钙调蛋白，可影响三种已知的哺乳动物RyR亚型的通道活性。已知RyRs对氧化还原有反应。然而，RyRs氧化还原调节的分子基础和生理相关性尚不清楚。最近的证据表明，一氧化氮（NO）及相关分子可能是骨骼肌和心肌RyRs的内源性调节剂。这两种组织表达一氧化氮合酶（NOSs），并且已表明NO或NO相关物质可通过硫醇基团的共价修饰直接影响Ca2+释放通道活性。已经描述了RyRs的氧化修饰和亚硝化修饰，导致RyR离子通道活性的可逆或不可逆改变。其他调节机制可能包括环鸟苷酸依赖性信号通路以及NO对RyR调节蛋白（如表面膜L型Ca2+通道）的修饰。NO对RyRs的修饰可能影响多种生理功能，如胰岛素释放、血管舒缩控制和肌肉收缩。
