https://scholars.lib.ntu.edu.tw/handle/123456789/563972
標題: | Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations | 作者: | Hsueh C.-H. WEN-PIN CHEN JIUNN-LEE LIN CHIA-TI TSAI YEN BIN LIU JYH-MING JIMMY JUANG Tsao H.-M. MING-JAI SU LING-PING LAI |
公開日期: | 2009 | 卷: | 16 | 期: | 1 | 起(迄)頁: | 23 | 來源出版物: | Journal of Biomedical Science | 摘要: | The Brugada syndrome is characterized by ST segment elevation in the right precodial leads V1-V3 on surface ECG accompanied by episodes of ventricular fibrillation causing syncope or even sudden death. The molecular and cellular mechanisms that lead to Brugada syndrome are not yet completely understood. However, SCN5A is the most well known responsible gene that causes Brugada syndrome. Until now, more than a hundred mutations in SCN5A responsible for Brugada syndrome have been described. Functional studies of some of the mutations have been performed and show that a reduction of human cardiac sodium current accounts for the pathogenesis of Brugada syndrome. Here we reported three novel SCN5A mutations identified in patients with Brugada syndrome in Taiwan (p.I848fs, p.R965C, and p.1876insM). Their electrophysiological properties were altered by patch clamp analysis. The p.I848fs mutant generated no sodium current. The p.R965C and p.1876insM mutants produced channels with steady state inactivation shifted to a more negative potential (9.4 mV and 8.5 mV respectively), and slower recovery from inactivation. Besides, the steady state activation of p.1876insM was altered and was shifted to a more positive potential (7.69 mV). In conclusion, the SCN5A channel defect related to Brugada syndrome might be diverse but all resulted in a decrease of sodium current. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/563972 | ISSN: | 10217770 | DOI: | 10.1186/1423-0127-16-23 | SDG/關鍵字: | sodium channel; muscle protein; SCN1B protein, human; SCN5A protein, human; sodium channel; article; Brugada syndrome; controlled study; disease association; electrophysiology; gene inactivation; gene mutation; human; human cell; human tissue; mutant; mutational analysis; patch clamp; priority journal; sodium current; Taiwan; Brugada syndrome; cell line; channel gating; electrocardiography; genetics; metabolism; mutation; nucleotide sequence; pathophysiology; site directed mutagenesis; Syncope; Brugada Syndrome; Cell Line; DNA Mutational Analysis; Electrocardiography; Humans; Ion Channel Gating; Muscle Proteins; Mutagenesis, Site-Directed; Mutation; Patch-Clamp Techniques; Sodium Channels; Taiwan |
顯示於: | 藥理學科所 |
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