Investigation of the pathomechanism of myotonic syndromes-Na channel disorders of skeletal muscle and myotonic dystrophy

强直性肌强直综合征-骨骼肌Na通道障碍与强直性肌营养不良发病机制的探讨

• 批准号: 20590998
• 负责人: TAKAHASHI Masanori
• 金额: $ 2.91万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590998/
• 关键词: 筋疾患; ナトリウムチャネル; イオンチャネル; 骨格筋; シミュレーション; パッチクランプ; mRNA; スプライシング; スプライジング; チャネル病; 筋疾患; ナトリウムチャネル; イオンチャネル; 骨格筋; シミュレーション; パッチクランプ; mRNA; スプライシング; スプライジング; チャネル病

Pathomechanism of myotonic syndromes (Na channel disorders of skeletal muscle and myotonic dystrophy) were investigated. Regarding the Na channel disorders of skeletal muscle, the channel function of novel mutations identified in Japanese patients were electrophysiologically analyzed and computer simulation were performed to elucidate pathophysiological mechanism. It should be noted that we identified a first case of non-dystrophic myotonia caused by a mutation in intron and revealed its molecular mechanism. Regarding myotonic dystrophy which is recently hypothesized as "mRNA disease", missplicing of an ion channel mRNA which might be linked to arrhythmia was identified in cardiac muscle.

研究了肌发综合征（NA通道疾病的骨骼肌和肌发育症）的病理力学。关于骨骼肌的NA通道障碍，对日本患者鉴定出的新型突变的通道功能进行了电生理分析，并进行了计算机模拟以阐明病理生理机制。应该注意的是，我们确定了由内含子突变引起的第一种非疾病性肌瘤的病例，并揭示了其分子机制。关于最近被假设为“ mRNA疾病”的肌发育症，在心脏肌肉中发现了可能与心律不齐有关的离子通道mRNA的错失。