Yudkowsky M L, Beech J, Fletcher J E
Department of Anesthesiology, Hahnemann University, Philadelphia, PA 19102.
Toxicon. 1994 Mar;32(3):273-8. doi: 10.1016/0041-0101(94)90080-9.
Myotoxin a, isolated from the venom of the prairie rattlesnake Crotalus viridis viridis, induces necrosis in skeletal muscle. In isolated organelles, it has been reported that myotoxin a reduces Ca2+ uptake into the sarcoplasmic reticulum. The effects of the toxin on Ca2+ regulation were examined in heavy sarcoplasmic reticulum fractions from human and equine skeletal muscle. Ca2+ uptake and release (the threshold of Ca(2+)-induced Ca2+ release) were examined by dual wavelength spectrophotometry. The toxin lowered the threshold of Ca(2+)-induced Ca2+ release in a dose-dependent manner (1-10 microM) and this effect was antagonized by ruthenium red, a Ca2+ release channel blocker. Ca2+ uptake into equine heavy sarcoplasmic reticulum was not decreased by myotoxin a (10 microM) when Ca2+ release was blocked by ruthenium red. [3H]Ryanodine binding to equine heavy sarcoplasmic reticulum was converted from a relatively low affinity state to a higher affinity state by myotoxin a. These results suggest that the dominant effect of myotoxin a is to increase the Ca2+ sensitivity for the opening of the calcium release channel (ryanodine receptor). Myotoxin a may prove to be a useful tool to probe the modulation of calcium release in sarcoplasmic reticulum fractions.
从草原响尾蛇绿曼巴蛇毒液中分离出的肌毒素a可诱导骨骼肌坏死。在分离的细胞器中，据报道肌毒素a可减少肌浆网对Ca2+的摄取。在人及马骨骼肌的重肌浆网部分检测了该毒素对Ca2+调节的影响。通过双波长分光光度法检测Ca2+摄取和释放（Ca2+诱导的Ca2+释放阈值）。该毒素以剂量依赖方式（1-10 microM）降低Ca2+诱导的Ca2+释放阈值，且该作用被Ca2+释放通道阻滞剂钌红所拮抗。当钌红阻断Ca2+释放时，肌毒素a（10 microM）并未降低马重肌浆网对Ca2+的摄取。肌毒素a可使[3H]ryanodine与马重肌浆网的结合从相对低亲和力状态转变为高亲和力状态。这些结果表明，肌毒素a的主要作用是增加钙释放通道（ryanodine受体）开放对Ca2+的敏感性。肌毒素a可能被证明是一种用于探究肌浆网部分钙释放调节的有用工具。
