Ionic current basis of electrocardiographic waveforms: a model study.
Body surface electrocardiograms and electrograms recorded from the surfaces of the heart are the basis for diagnosis and treatment of cardiac electrophysiological disorders and arrhythmias. Given recent advances in understanding the molecular mechanisms of arrhythmia, it is important to relate these electrocardiographic waveforms to cellular electrophysiological processes. This modeling study establishes the following principles: (1) voltage gradients created by heterogeneities of the slow-delayed rectifier (I(Ks)) and transient outward (I(to)) potassium current inscribe the T wave and J wave, respectively; T-wave polarity and width are strongly influenced by the degree of intercellular coupling through gap-junctions. (2) Changes in [K+]o modulate the T wave through their effect on the rapid-delayed rectifier, I(Kr). (3) Alterations of I(Ks), I(Kr), and I(Na) (fast sodium current) in long-QT syndrome (LQT1, LQT2, and LQT3, respectively) are reflected in characteristic QT-interval and T-wave changes; LQT1 prolongs QT without widening the T wave. (4) Accelerated inactivation of I(Na) on the background of large epicardial I(to) results in ST elevation (Brugada phenotype) that reflects the degree of severity. (5) Activation of the ATP-sensitive potassium current, I(K(ATP)), is sufficient to cause ST elevation during acute ischemia. These principles provide a mechanistic cellular basis for interpretation of electrocardiographic waveforms.
Gima
Kazutaka
K
Cardiac Bioelectricity Research and Training Center, Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106-7207, USA.
Rudy
Yoram
Y
D000200:Action Potentials; D001145:Arrhythmias, Cardiac / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D004553:Electric Conductivity; D004562:Electrocardiography; D017629:Gap Junctions / Q000502:physiology; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D017136:Ion Transport; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D008955:Models, Cardiovascular; D008962:Models, Theoretical; D009154:Mutation; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000235:genetics; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology; D013577:Syndrome
D007473:Ion Channels; D015221:Potassium Channels; D011188:Potassium