Louis C F, Balog E M, Fruen B R
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis 55455, USA.
Biosci Rep. 2001 Apr;21(2):155-68. doi: 10.1023/a:1013644107519.
Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle characterized by muscle contracture and life-threatening hypermetabolic crisis following exposure to halogenated anesthetics and depolarizing muscle relaxants during surgery. Susceptibility to MH results from mutations in Ca2+ channel proteins that mediate excitation-contraction (EC) coupling, with the ryanodine receptor Ca2+ release channel (RyRI) representing the major locus. Here we review recent studies characterizing the effects of MH mutations on the sensitivity of the RyRI to drugs and endogenous channel effectors including Ca2+ and calmodulin. In addition, we present a working model that incorporates these effects of MH mutations on the isolated RyRI with their effects on the physiologic mechanism that activates Ca2+ release during EC coupling in intact muscle.
恶性高热（MH）是一种骨骼肌的药物遗传学疾病，其特征为在手术期间接触卤化麻醉剂和去极化肌肉松弛剂后出现肌肉挛缩和危及生命的高代谢危机。MH易感性源于介导兴奋-收缩（EC）偶联的Ca2+通道蛋白发生突变，其中兰尼碱受体Ca2+释放通道（RyRI）是主要位点。在此，我们综述了最近的研究，这些研究描述了MH突变对RyRI对药物和内源性通道效应器（包括Ca2+和钙调蛋白）敏感性的影响。此外，我们提出了一个工作模型，该模型将MH突变对分离的RyRI的这些影响与其对完整肌肉中EC偶联期间激活Ca2+释放的生理机制的影响结合起来。
