骨格筋Naチャネル遺伝子変異と家族性周期性四肢麻痺

• 杉浦 嘉泰

  福島県立医大・医・神経内科

書誌事項

タイトル別名

• Periodic paralysis caused by skeletal muscle sodium channelopathies

抄録

We reported a dominantly inherited Japanese family with myotonia and cold-induced hypokalemic periodic paralysis. The proband showed hypokalemia and flaccid paralysis in cold atmospheric temperatures. This phenotype is associated with a novel mutation in the voltage dependent skeletal muscle sodium channel (Na_v1.4) alpha subunit gene (SCN4A). This P1158S mutation is localized between the fourth and fifth transmembrane segments of domain III in Na_v1.4. Using the amphotericin B-perforated-patch clamp method, sodium currents were recorded at 22°C and 32°C from the wild type (WT) and P1158S mutant Na_v1.4 expressed in tsA201 cells. Computer simulation was performed incorporating the gating-parameters of the P1158S mutant Na_v1.4. P1158S mutant Na_v1.4 exhibited hyperpolarizing shifts in voltage-dependence of both activation and inactivation curves at a cold temperature and a slower rate of inactivation than the WT. Computer simulation reproduced the abnormal skeletal muscle electrical activities of both paralysis at a low potassium concentration in the cold, and myotonia at a normal potassium concentration. For the first time we found that a single amino acid mutant sodium channel shifted the voltage dependency in the hyperpolarizing direction in a temperature dependent manner. Recently, it was reported that generalized epilepsy with febrile seizures plus (GEFS+) were caused by sodium channel mutations, and the heat-induced paralysis of the smellblind drosophila mutant was also found to be due to a sodium channel mutation. Thus, sodium channel abnormalities may be responsible for the temperature sensitive pathological states of various diseases. [Jpn J Physiol 55 Suppl:S7 (2005)]

収録刊行物

• 日本生理学会大会発表要旨集

  日本生理学会大会発表要旨集 2005 (0), S7-S7, 2005

  一般社団法人　日本生理学会

キーワード

• periodic paralysis
• myotonia
• temperature dependency
• SCN4A
• Nav1.4

詳細情報

• CRID: 1390282680704901760
• NII論文ID: 130005448023
• DOI: 10.14849/psjproc.2005.0_s7_3
• データソース種別:
  • JaLC
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可