title: Excitation-contraction coupling gain in ventricular myocytes: insights from a parsimonious model.
abstract: We present a minimal mathematical model of Ca(2+) spark triggering under voltage-clamp conditions in ventricular myocytes. The model predicts changes in excitation-contraction coupling 'gain' that result from diverse experimental interventions. We compare model results to several sets of data, and, in so doing, place apparent constraints on physiologically relevant model parameters. Specifically, the analysis suggests that many L-type Ca(2+) channel openings can potentially trigger each Ca(2+) spark, but the probability that an individual opening will trigger a spark is low. This procedure helps to reconcile contradictory results obtained in recent studies; moreover, this new model should be a useful tool for understanding changes in gain that occur physiologically and in disease.
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY, USA. eric.sobie@mssm.edu
authors.forename: Eric A
authors.initials: EA
authors.lastname: Sobie
authors.forename: Hena R
authors.initials: HR
authors.lastname: Ramay
mesh_terms: D000465:Algorithms; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D003198:Computer Simulation; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D018408:Patch-Clamp Techniques
chemical_list: D020746:Calcium Channels, L-Type