筋チャネル病の病態解析

抄録

Skeletal muscle channelopathies are rare genetic disorders caused by mutations in voltage-gated ion channel genes regulating the excitability of the sarcomere. In SCN4A gene coding for Nav1.4, the skeletal muscle type voltage-gated sodium channel, more than one hundred heterozygous missense mutations have been identified so far, which represent broad clinical phenotype including sodium channel myotonia (SCM), paramyotonia congenita (PMC), hyperkalemic periodic paralysis (HyperPP) and hypokalemic periodic paralysis (HypoPP). In addition, recent case reports showed that hetero-compound mutations or homozygous mutations in SCN4A are associated with congenital myopathy or congenital myasthenic syndrome. Many electrophysiological analyses revealed an association between functional alteration of the mutant Nav1.4 and clinical phenotype. On the other hand, there is little progress in the discovery of the therapeutics. Recently, we have generated HEK293T-based HypoPP-model cell lines aiming to establish the in vitro platform for the high-throughput drug screen. Our HypoPP-model cells would give a new insight to develop novel therapeutics for channelopathy.