The interaction of the membrane and calcium oscillators in cardiac pacemaker cells: Mathematical modeling

An integrative model of the calcium dynamics in cardiac pacemaker cells is developed taking the synergetic effect of the coupling of the membrane and the intracellular calcium oscillators (“membrane and Ca 2+ clock”) into account. The main feature of the model is a description of the stochastic dynamics of Ca 2+ release units within the electron-conformational dynamics of ryanodine channels (RyR-channels). It is shown that interaction of the cellular oscillators provides stable action-potential generation in cardiac pacemaker cells, even in the case of stochastic Ca 2+ dynamics. We studied the effect of RyR sensitivity to the intracellular calcium concentration in the sarcoplasmic reticulum and in the dyadic space on the behavior of the calcium-release system in detail. A parametric analysis of an integrative model of pacemaker cells was performed.