Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations

Chia Hsiang Hsueh, Wen Pin Chen, Jiunn Lee Lin, Chia Ti Tsai, Yen Bin Liu, Jyh Ming Juang, Hsuan Ming Tsao, Ming Jai Su, Ling Ping Lai

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number23
JournalJournal of Biomedical Science
Volume16
Issue number1
DOIs
Publication statusPublished - Apr 9 2009
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations'. Together they form a unique fingerprint.

  • Cite this

    Hsueh, C. H., Chen, W. P., Lin, J. L., Tsai, C. T., Liu, Y. B., Juang, J. M., Tsao, H. M., Su, M. J., & Lai, L. P. (2009). Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations. Journal of Biomedical Science, 16(1), [23]. https://doi.org/10.1186/1423-0127-16-23