Calcium signals perform integral roles in cardiac cells, coordinating each heartbeat, and regulating the biochemical reactions that control growth. Inositol 1,4,5-triphosphate receptors (IP3Rs) are intracellular calcium channels that are known to influence these processes during cellular hypertrophy. Recent protein localization experiments suggest IP3Rs may exist in close proximity to ryanodine receptors (RyRs), the channels primarily responsible for the flood of calcium from intracellular stores (sparks) during calcium-induced calcium release. In this study, we seek to untangle the contribution of IP3Rs to spark formation. We develop mathematical models incorporating the stochastic behavior of opening receptors that allow for the parametric tuning of the system to reveal the impact of IP3Rs on spark activation. By testing multiple spark initiation mechanisms, we find that consistently opening (“leaky”) IP3Rs can result in spark initiation more reliably than intermittently opening IP3Rs. We also find that while increasing numbers of IP3Rs increase the probability of formation of a spark, they have little impact on its resultant amplitude, duration, or overall shape.
