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1 Department of Biomedical Sciences and 2 Department of Physics, Cornell University, Ithaca, New York 14853-6401
Although alternans of action potential duration (APD) is a robust feature of the rapidly paced canine ventricle, currently available ionic models of cardiac myocytes do not recreate this phenomenon. To address this problem, we developed a new ionic model using formulations of currents based on previous models and recent experimental data. Compared with existing models, the inward rectifier K+ current (IK1) was decreased at depolarized potentials, the maximum conductance and rectification of the rapid component of the delayed rectifier K+ current (IKr) were increased, and IKr activation kinetics were slowed. The slow component of the delayed rectifier K+ current (IKs) was increased in magnitude and activation shifted to less positive voltages, and the L-type Ca2+ current (ICa) was modified to produce a smaller, more rapidly inactivating current. Finally, a simplified form of intracellular calcium dynamics was adopted. In this model, APD alternans occurred at cycle lengths = 150-210 ms, with a maximum alternans amplitude of 39 ms. APD alternans was suppressed by decreasing ICa magnitude or calcium-induced inactivation and by increasing the magnitude of IK1, IKr, or IKs. These results establish an ionic basis for APD alternans, which should facilitate the development of pharmacological approaches to eliminating alternans.
action potential duration restitution; calcium current; potassium currents
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