Ionic mechanism of electrical alternans

Abstract

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 ( I K1) was decreased at depolarized potentials, the maximum conductance and rectification of the rapid component of the delayed rectifier K+ current ( I Kr) were increased, and I Kr activation kinetics were slowed. The slow component of the delayed rectifier K+current ( I Ks) was increased in magnitude and activation shifted to less positive voltages, and the L-type Ca2+ current ( I Ca) 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 I Ca magnitude or calcium-induced inactivation and by increasing the magnitude of I K1, I Kr, or I Ks. These results establish an ionic basis for APD alternans, which should facilitate the development of pharmacological approaches to eliminating alternans.