Calcium sparks are a manifestation of a functioning of the intracellular calcium release system, which can operate as a self-sustaining oscillator (clock). Disturbances in Ca2+ sparks formation can be an arrhythmogenic factor in a pacemaker cell.
We introduce results of simulations of calcium sparks. We developed a model of the calcium release unit which includes a single sarcoplasmic reticulum lumen, a regular 9x9 cluster of RyRs and a dyadic space. 2D diffusion problem of Ca2+ ions across the dyadic space was solved thereby we reproduced Calcium-Induced-Calcium-Release effect and “domino-like” RyRs activation. We used the finite differences method to solve the 2D problem of Ca2+ diffusion which is described by the standard diffusion equation. Parameters of Ca2+ dynamics were taken from Maltsev-Lakatta model (Maltsev et al., AmJPhys, 2009). RyRs’ dynamics in the cluster is described by equations of developed earlier RyR Electron-Conformational model (ECM) (Moskvin et al., PBMB, 2006). This approach allows taking into account conformational coupling between RyRs. Earlier it was shown that conformational coupling between RyRs causes a stability of isolated from the membrane intracellular Ca2+ clock (Ryvkin, et al., Biophysics, 2015). However a sufficiently strong RyR-RyR coupling can be a reason of a “Ca2+-clock sudden stop effect” which is manifested in an occasional forming of a stable open RyRs cluster (2x2, 3x3, etc.) through which a stable Ca2+ leak occurs. A similar effect we observed in case of Ca2+ RyR-RyR interaction. This regime manifests itself in the opening of a certain number of channels in a small region. Diffusion supports channels in an open state, but spark does not propagate further. This regime is manifested at a sufficiently low diffusion rate of Ca2+ along the dyadic space and can explain a number of arrhythmogenic effects associated with disorders in the intracellular Ca2+ -release system. Supp. RFBR grant 16-34-60223.