title: A model study of propagation of early afterdepolarizations.
abstract: Early afterdepolarizations (EAD's) are irregularities of the cardiac action potential that interrupt or retard repolarization. EAD's have been linked to the development of specific types of cardiac arrhythmias, however, the mechanism underlying the development of these arrhythmias remains unclear. We implemented a two-element kinetic model of the ventricular action potential to investigate a potentially arrhythmogenic form of triggered activity. By approximating EAD's by a sinusoidal driving force, we were able to study the effects of interelement coupling resistivity and sinusoidal frequency and amplitude on the triggering of action potentials. We demonstrated EAD's in a ventricular action potential model by altering the potassium and calcium channels to simulate experimental conditions under which EAD's occur. We also found that triggered activity depends critically on the frequency and amplitude of the driving force and also on the degree of cellular uncoupling between the elements. Our results suggest that triggered activity (due to EAD's) may be suppressed by drugs that improve coupling in unhealthy tissue, or ones that prevent EAD formation by inhibiting calcium channels.
authors.affiliation: Department of Medicine, University of California, San Francisco, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Wagner
authors.forename: W J
authors.initials: WJ
authors.lastname: Gibb
authors.forename: M D
authors.initials: MD
authors.lastname: Lesh
mesh_terms: D000200:Action Potentials / Q000502:physiology; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology; D015220:Calcium Channels / Q000502:physiology; D006321:Heart / Q000502:physiology*; D006801:Humans; D008433:Mathematics; D008955:Models, Cardiovascular; D015221:Potassium Channels / Q000502:physiology; D013997:Time Factors; D016276:Ventricular Function
chemical_list: D015220:Calcium Channels; D015221:Potassium Channels