simulation of the undiseased human cardiac ventricular action potential model formulation and experimental validation模拟人类心脏心室undiseased动作电位模型公式和实验验证.pdfVIP

Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation 1 ´ ´ ´ 2 ´ ´ 2,3 1 Thomas O’Hara , Laszlo Virag , Andras Varro , Yoram Rudy * 1 Cardiac Bioelectricity and Arrhythmia Center, Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, United States of America, 2 Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary, 3 Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary Abstract Cellular electrophysiology experiments, important for understanding cardiac arrhythmia mechanisms, are usually performed with channels expressed in non myocytes, or with non-human myocytes. Differences between cell types and species affect results. Thus, an accurate model for the undiseased human ventricular action potential (AP) which reproduces a broad range of physiological behaviors is needed. Such a model requires extensive experimental data, but essential elements have been unavailable. Here, we develop a human ventricular AP model using new undiseased human ventricular data: Ca2+ versus voltage dependent inactivation of L-type Ca2+ current (ICaL); kinetics for the transient outward, rapid delayed rectifier (IKr), Na+/Ca2+ exchange (INaCa), and inward rectifier currents; AP recordings at all physiological cycle lengths; and rate dependence and restitution of AP duration (APD) with and without a variety of specific channel blockers. Simulated APs reproduced the experimental AP morphology, APD rate dependence, and restitution. Using undiseased human mRNA and protein data, models for different transmural cell types were developed. Experiments for rate