From Genome to Physiome: Integrative Models of Cardiac Excitation

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• 作者：Yoram Rudy
• 关键词：Cardiac arrhythmia ; Genetic mutation ; Long QT syndrome ; Cardiac action potential ; Ion channels ; Gap junctions ; Slow conduction
• 刊名：Annals of Biomedical Engineering
• 出版年：2000
• 出版时间：August 2000
• 年：2000
• 卷：28
• 期：8
• 页码：945-950
• 全文大小：536 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Biomedicine
  Biomedical Engineering
  Biophysics and Biomedical Physics
  Mechanics
  Biochemistry
  
• 出版者：Springer Netherlands
• ISSN：1573-9686

文摘

The last decade has generated extensive information on the genetic and molecular basis of disease. A major challenge remains the integration of this information into the physiological environment of the functioning cell and tissue. This article illustrates the use of computational biology in meeting this challenge in the context of cardiac excitation and arrhythmia. (1) Genetics to Cell Function: Mutations that alter the kinetics of the cardiac sodium channel, I_Na, give rise to a congenital form of the long QT syndrome that can lead to sudden death. Using a computer model of the cardiac cell, we simulated the effects of the mutations on the action potential, demonstrating its prolongation at slow rate and the development of arrhythmogenic early afterdepolarizations due to reactivation of L-type Ca channels, I_Ca(L) [Clancy and Rudy, Nature (London)400:566, 1999]. (2) Multicellular Tissue: Slow conduction is an important property of propagation arrhythmias (reentry). Very slow conduction is supported by reduced intercellular coupling through gap junctions. Using a multicellular fiber model, we have shown that slow conduction is very stable and, in contrast to normal conduction which depends solely on I_Na requires a major contribution from I_Ca(L) (Shaw and Rudy, Circ. Res.81:727, 1997). © 2000 Biomedical Engineering Society.PAC00: 8719Hh, 8719Nn, 8717Nn, 8710+e