title: Computer model of action potential of mouse ventricular myocytes.
abstract: We have developed a mathematical model of the mouse ventricular myocyte action potential (AP) from voltage-clamp data of the underlying currents and Ca2+ transients. Wherever possible, we used Markov models to represent the molecular structure and function of ion channels. The model includes detailed intracellular Ca2+ dynamics, with simulations of localized events such as sarcoplasmic Ca2+ release into a small intracellular volume bounded by the sarcolemma and sarcoplasmic reticulum. Transporter-mediated Ca2+ fluxes from the bulk cytosol are closely matched to the experimentally reported values and predict stimulation rate-dependent changes in Ca2+ transients. Our model reproduces the properties of cardiac myocytes from two different regions of the heart: the apex and the septum. The septum has a relatively prolonged AP, which reflects a relatively small contribution from the rapid transient outward K+ current in the septum. The attribution of putative molecular bases for several of the component currents enables our mouse model to be used to simulate the behavior of genetically modified transgenic mice.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York 14214-3078, USA.
authors.forename: Vladimir E
authors.initials: VE
authors.lastname: Bondarenko
authors.forename: Gyula P
authors.initials: GP
authors.lastname: Szigeti
authors.forename: Glenna C L
authors.initials: GC
authors.lastname: Bett
authors.forename: Song-Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Randall L
authors.initials: RL
authors.lastname: Rasmusson
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology; D018118:Chloride Channels / Q000502:physiology; D003198:Computer Simulation; D051668:Delayed Rectifier Potassium Channels; D004553:Electric Conductivity; D006706:Homeostasis; D051379:Mice; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D015222:Sodium Channels / Q000502:physiology; D016276:Ventricular Function
chemical_list: D020746:Calcium Channels, L-Type; D018118:Chloride Channels; D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015222:Sodium Channels; D002118:Calcium