Mathematical modeling shows the frequency of Ca2+ sparks in cells depends on the ryanodine receptor's arrangement

Calcium dynamics plays key role in many intracellular processes. Studying of calcium sparks, that is events of calcium release via groups of ryanodine receptors, or RyR channels, is of a great importance for live sciences. Recent experimental studies show, that RyRs have a non-uniform arrangement in calcium release units (CRU), however, to our knowledge, there is yet no published Ca2+ spark model which takes into account this fact. In the paper we made use of a genetic simulated annealing (GSA) algorithm for the RyR cluster generation and Gillespie algorithm for modeling calcium spark. Computer simulation of the model CRU taking into account a specific homotetrameric structure of the RyR channel shows that experimental nearest neighbor distances (NND) distributions of RyRs in CRU do not provide exact information about calcium spark probability. Having the same NND distribution, the CRUs can have different inverse distance matrices and hence different calcium spark properties. Our model approach opens novel perspectives for studying the calcium release process.