title: Interplay of ryanodine receptor distribution and calcium dynamics.
abstract: Spontaneously generated calcium (Ca2+) waves can trigger arrhythmias in ventricular and atrial myocytes. Yet, Ca2+ waves also serve the physiological function of mediating global Ca2+ increase and muscle contraction in atrial myocytes. We examine the factors that influence Ca2+ wave initiation by mathematical modeling and large-scale computational (supercomputer) simulations. An important finding is the existence of a strong coupling between the ryanodine receptor distribution and Ca2+ dynamics. Even modest changes in the ryanodine receptor spacing profoundly affect the probability of Ca2+ wave initiation. As a consequence of this finding, we suggest that there is information flow from the contractile system to the Ca2+ control system and this dynamical interplay could contribute to the increased incidence of arrhythmias during heart failure.
authors.affiliation: Department of Internal Medicine, University of Kentucky, School of Medicine, Lexington, Kentucky 40536-0509, USA. leightonizu@uky.edu
authors.forename: Leighton T
authors.initials: LT
authors.lastname: Izu
authors.forename: Shawn A
authors.initials: SA
authors.lastname: Means
authors.forename: John N
authors.initials: JN
authors.lastname: Shadid
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen-Izu
authors.forename: C William
authors.initials: CW
authors.lastname: Balke
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D003198:Computer Simulation; D007700:Kinetics; D008657:Metabolic Clearance Rate; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium