Modelling and imaging cardiac repolarization abnormalities.
Repolarization abnormalities, including those induced by the congenital or acquired long QT (LQT) syndrome, provide a substrate for life-threatening cardiac arrhythmias. In this article, we use computational biology to link HERG mutations mechanistically to the resulting abnormalities of the whole-cell action potential. We study how the kinetic properties of I(Ks) (the slow delayed rectifier) that are conferred by molecular subunit interactions, facilitate its role in repolarization and 'repolarization reserve'. A new noninvasive imaging modality (electrocardiographic imaging) is shown to image cardiac repolarization on the epicardial surface, suggesting its possible role in risk stratification, diagnosis and treatment of LQT syndrome.
Rudy
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Cardiac Bioelectricity and Arrhythmia Center (CBAC), Washington University in St Louis, St Louis, MO 63130-4899, USA. rudy@wustl.edu
D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D000222:Adaptation, Physiological; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000503:physiopathology*; D003198:Computer Simulation; D004195:Disease Models, Animal; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000502:physiology; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology*; D008133:Long QT Syndrome / Q000235:genetics / Q000503:physiopathology; D008390:Markov Chains; D008968:Molecular Conformation; D009154:Mutation; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology; D018570:Risk Assessment / Q000379:methods
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D015221:Potassium Channels