Excitation-contraction coupling gain in ventricular myocytes: Insights from a parsimonious model

We present a minimal mathematical model of Ca²⁺ 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 Ca²⁺ channel openings can potentially trigger each Ca²⁺ 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.