Link between SCN5A mutation and the Brugada syndrome ECG phenotype: Simulation study

Shunichiro Miyoshi, Hideo Mitamura, Yukiko Fukuda, Kojiro Tanimoto, Yoko Hagiwara, Hideaki Kanki, Seiji Takatsuki, Mitsushige Murata, Toshihisa Miyazaki, Satoshi Ogawa

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


Background: The specific changes in the gating kinetics of the sodium current (INa) responsible for its phenotype have remained to be elucidated. In the present study the effect of changes in the gating kinetics of INa on early repolarization (ER) and initiation of phase 2 reentry (P2R) were evaluated in a theoretical epicardial ventricular fiber model. Methods and Results: Miyoshi-ICaL was incorporated into the modified Luo-Rudy dynamic (LRd) model. Dispersion at Ito-density was set within a theoretical fiber composed of serially arranged epicardial cells with gap junctions. The following changes in INa kinetics were made: (1) a -10mV shift in steady-state inactivation, (2) a +10mV shift in steady-state activation curve, (3) a small inactivation time constant (DEC); P2R and ER were observed. A conduction disturbance within the fiber was simulated and only when the INa-density was decreased did DEC, especially, show a marked increase in the likelihood of causing ER and P2R. Conduction disturbance significantly increased the likelihood causing ER or P2R. Conclusions: In this one-dimension model with Ito-density dispersion, DEC-INa precipitates INa-blocker inducible ER. This suggests that the characteristic ST-segment elevation in the Brugada syndrome with SCN5A mutation can be interpreted in part by DEC-INa. Concomitant conduction disturbance may be required to cause P2R at physiological Ito density.

Original languageEnglish
Pages (from-to)567-575
Number of pages9
JournalCirculation Journal
Issue number5
Publication statusPublished - 2005 May


  • Arrhythmia
  • Computers
  • Electrocardiogram
  • Electrophysiology
  • Ventricles

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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