Parameter sensitivity analysis of stochastic models provides insights into cardiac calcium sparks.

We present a parameter sensitivity analysis method that is appropriate for stochastic models, and we demonstrate how this analysis generates experimentally testable predictions about the factors that influence local Ca(2+) release in heart cells. The method involves randomly varying all parameters, running a single simulation with each set of parameters, running simulations with hundreds of model variants, then statistically relating the parameters to the simulation results using regression methods. We tested this method on a stochastic model, containing 18 parameters, of the cardiac Ca(2+) spark.

Decoding myocardial Ca²⁺ signals across multiple spatial scales: a role for sensitivity analysis.

Numerous studies have employed mathematical modeling to quantitatively understand release of Ca(2+) from the sarcoplasmic reticulum (SR) in the heart. Models have been used to investigate physiologically important phenomena such as triggering of SR Ca(2+) release by Ca(2+) entry across the cell membrane and spontaneous leak of Ca(2+) from the SR in quiescent heart cells. In this review we summarize studies that have modeled myocardial Ca(2+) at different spatial scales: the sub-cellular level, the cellular level, and the multicellular level.

Recovery of cardiac calcium release is controlled by sarcoplasmic reticulum refilling and ryanodine receptor sensitivity.

Aims: In heart cells, the mechanisms underlying refractoriness of the elementary units of sarcoplasmic reticulum (SR) Ca(2+) release, Ca(2+) sparks, remain unclear. We investigated local recovery of SR Ca(2+) release using experimental measurements and mathematical modelling.

Methods And Results: Repeated Ca(2+) sparks were induced from individual clusters of ryanodine receptors (RyRs) in quiescent rat ventricular myocytes, and we examined how changes in RyR gating influenced the time-dependent recovery of Ca(2+) spark amplitude and triggering probability.