Electrical myotonia of rabbit skeletal muscles by HMG-CoA reductase inhibitors

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.