- 作者: 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
- 作者服務機構: Institute of Pharmacology, School of Medicine, National Taiwan University, Taipei, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
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 (9.4mV and 8.5mV respectively), and slower recovery from
inactivation. Besides, the steady state activation of p.1876insM was altered and was
shifted to a more positive potential (7.69mV). In conclusion, the SCN5A channel
defect related to Brugada syndrome might be diverse but all resulted in a decrease of
sodium current. - 中文關鍵字: --
- 英文關鍵字: --