Ionic mechanism of electrical alternans

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 thi...

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Bibliographic Details
Published in:American journal of physiology. Heart and circulatory physiology 2002-02, Vol.282 (2), p.H516-H530
Main Authors: Fox, Jeffrey J, McHarg, Jennifer L, Gilmour, Robert F., Jr
Format: Article
Language:English
Subjects:
Action Potentials - physiology
Animals
Calcium - metabolism
Calcium Channels, L-Type - physiology
Diastole - physiology
Dogs
Heart - physiology
Models, Cardiovascular
Muscle Fibers, Skeletal - physiology
Myocardium - cytology
Potassium - metabolism
Potassium Channels - physiology
Potassium Channels, Inwardly Rectifying
Sodium - metabolism
Sodium Channels - physiology
Ventricular Fibrillation - physiopathology
Ventricular Function
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Summary: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 ( 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 Ca 2+ 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. action potential duration restitution; calcium current; potassium currents
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.00612.2001