Sonoda Y, Gotow T, Kuriyama M, Nakahara K, Arimura K, Osame M
Third Department of Internal Medicine, Kagoshima University School of Medicine, Japan.
Muscle Nerve. 1994 Aug;17(8):891-7. doi: 10.1002/mus.880170808.
HMG-CoA reductase (HCR) inhibitors are effective cholesterol-lowering agents in the treatment of hypercholesterolemia. Using intracellular microelectrodes, we studied the pathomechanism of myotonia experimentally induced in rabbits by HCR inhibitors, simvastatin, and pravastatin. The external intercostal muscle of rabbits showed some electrophysiologic characteristics of myotonia including repetitive firing after administration of simvastatin (50 mg/kg per day, for 4 weeks). The relative chloride conductance, though reduced in both, was more affected in simvastatin-administered muscles. In normal muscles perfused with a solution containing the inhibitors, both simvastatin and pravastatin produced membrane hyperexcitability with repetitive firing similar to that seen in simvastatin-administered rabbits. The minimum concentrations required to cause repetitive firing was 0.3 mg/L for simvastatin and 30 mg/L for pravastatin. These results indicate that HCR inhibitors induce some characteristics of myotonia by blocking the chloride channel in the muscle membrane.
HMG-CoA还原酶（HCR）抑制剂是治疗高胆固醇血症的有效降胆固醇药物。我们使用细胞内微电极，研究了HCR抑制剂辛伐他汀和普伐他汀在实验中诱导家兔肌强直的发病机制。家兔的肋间外肌表现出一些肌强直的电生理特征，包括在给予辛伐他汀（每天50mg/kg，持续4周）后出现重复放电。相对氯离子电导虽然在两者中均降低，但在给予辛伐他汀的肌肉中受影响更大。在用含有抑制剂的溶液灌注的正常肌肉中，辛伐他汀和普伐他汀均产生膜兴奋性增高并伴有重复放电，类似于在给予辛伐他汀的家兔中所见。引起重复放电所需的最低浓度，辛伐他汀为0.3mg/L，普伐他汀为30mg/L。这些结果表明，HCR抑制剂通过阻断肌膜中的氯离子通道诱导一些肌强直特征。
