title: In Silico Investigation into Cellular Mechanisms of Cardiac Alternans in Myocardial Ischemia.
abstract: Myocardial ischemia is associated with pathophysiological conditions such as hyperkalemia, acidosis, and hypoxia. These physiological disorders may lead to changes on the functions of ionic channels, which in turn form the basis for cardiac alternans. In this paper, we investigated the roles of hyperkalemia and calcium handling components played in the genesis of alternans in ischemia at the cellular level by using computational simulations. The results show that hyperkalemic reduced cell excitability and delayed recovery from inactivation of depolarization currents. The inactivation time constantτfof L-type calcium current (ICaL) increased obviously in hyperkalemia. One cycle length was not enough forICaLto recover completely. Alternans developed as a result ofICaLresponding to stimulation every other beat. Sarcoplasmic reticulum calcium-ATPase (SERCA2a) function decreased in ischemia. This change resulted in intracellular Ca (Cai) alternans of small magnitude. A strong Na+-Ca2+exchange current (INCX) increased the magnitude of Caialternans, leading to APD alternans through excitation-contraction coupling. Some alternated repolarization currents contributed to this repolarization alternans.
authors.affiliation: Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China.
authors.forename: Yinglan
authors.identifier: 0000-0003-1533-1446
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China.
authors.forename: Ling
authors.identifier: 0000-0002-1937-9693
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Mechanical, Aerospace, and Biomedical Engineering, University of Tennessee, Knoxville, TN 37996, USA.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D003198:Computer Simulation; D006801:Humans; D006947:Hyperkalemia / Q000378:metabolism / Q000503:physiopathology*; D007477:Ions; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000502:physiology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
chemical_list: D007477:Ions; D019831:Sodium-Calcium Exchanger; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D002118:Calcium