Link Between SCN5A Mutation and the Brugada Syndrome ECG Phenotype : Simulation Study

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Background The specific changes in the gating kinetics of the sodium current (I_<Na>) responsible for its phenotype have remained to be elucidated. In the present study the effect of changes in the gating kinetics of I_<Na> on early repolarization (ER) and initiation of phase 2 reentry (P2R) were evaluated in a theoretical epicardial ventricular fiber model. Methods and Results Miyoshi-I_<CaL> was incorporated into the modified Luo-Rudy dynamic (LRd) model. Dispersion at I_<to>-density was set within a theoretical fiber composed of serially arranged epicardial cells with gap junctions. The following changes in I_<Na> 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 I_<Na>-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 I_<to>-density dispersion, DEC-I_<Na> precipitates I_<Na>-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-I_<Na>. Concomitant conduction disturbance may be required to cause P2R at physiological I_<to> density.

収録刊行物

  • Circulation journal : official journal of the Japanese Circulation Society

    Circulation journal : official journal of the Japanese Circulation Society 69(5), 567-575, 2005-04-20

    社団法人日本循環器学会

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各種コード

  • NII論文ID(NAID)
    10015657926
  • NII書誌ID(NCID)
    AA11591968
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13469843
  • データ提供元
    CJP書誌  CJP引用  NII-ELS  J-STAGE 
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