title: Ca2+ alternans in a cardiac myocyte model that uses moment equations to represent heterogeneous junctional SR Ca2+.
abstract: Multiscale whole-cell models that accurately represent local control of Ca2+-induced Ca2+ release in cardiac myocytes can reproduce high-gain Ca2+ release that is graded with changes in membrane potential. Using a recently introduced formalism that represents heterogeneous local Ca2+ using moment equations, we present a model of cardiac myocyte Ca2+ cycling that exhibits alternating sarcoplasmic reticulum (SR) Ca2+ release when periodically stimulated by depolarizing voltage pulses. The model predicts that the distribution of junctional SR [Ca2+] across a large population of Ca2+ release units is distinct on alternating cycles. Load-release and release-uptake functions computed from this model give insight into how Ca2+ fluxes and stimulation frequency combine to determine the presence or absence of Ca2+ alternans. Our results show that the conditions for the onset of Ca2+ alternans cannot be explained solely by the steepness of the load-release function, but that changes in the release-uptake process also play an important role. We analyze the effect of the junctional SR refilling time constant on Ca2+ alternans and conclude that physiologically realistic models of defective Ca2+ cycling must represent the dynamics of heterogeneous junctional SR [Ca2+] without assuming rapid equilibration of junctional and network SR [Ca2+].
authors.affiliation: Department of Applied Science, College of William and Mary, Williamsburg, Virginia, USA. mhuer1@lsuhsc.edu
authors.forename: Marco A
authors.initials: MA
authors.lastname: Huertas
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Smith
authors.forename: Sándor
authors.initials: S
authors.lastname: Györke
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004285:Dogs; D006339:Heart Rate / Q000502:physiology*; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D013997:Time Factors
chemical_list: D002118:Calcium