ELECTRICAL MYOTONIA OF RABBIT SKELETAL-MUSCLES BY HMG-COA REDUCTASE INHIBITORS
ELECTRICAL MYOTONIA OF RABBIT SKELETAL-MUSCLES BY HMG-COA REDUCTASE INHIBITORS
复制标题
DOI：
10.1002/mus.880170808
复制
发表时间：
1994-08-01
期刊：
影响因子：
3.4
通讯作者：
OSAME, M
中科院分区：
文献类型：
--
作者：
SONODA, Y;GOTOW, T;OSAME, M
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。我们用细胞内微电极研究了HCR抑制剂、辛伐他汀和普伐他汀诱导的兔肌强直的发病机制。兔肋间外肌在给予辛伐他汀(50 mg/(kg·d)，连续4周)后，表现出肌强直的电生理特征，包括重复放电。尽管两者的相对氯离子电导都有所降低，但辛伐他汀对肌肉的影响更大。在灌流了含有抑制剂的溶液的正常肌肉中，辛伐他汀和普伐他汀都产生了膜的过度兴奋性，其重复放电与给予辛伐他汀的兔相似。引起重复点火的最低浓度：辛伐他汀为0.3 mg/L，普伐他汀为30 mg/L。这些结果表明，HCR抑制剂通过阻断肌膜上的氯通道而诱导肌强直的某些特征。(C)1994年John Wiley&Sons，Inc.
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. (C) 1994 John Wiley & Sons, Inc.