ABSTRACT
An integrative model of the calcium dynamics in cardiac pacemaker cells is developed taking into account a synergetic effect of the interaction between an outer membrane oscillator and an intracellular calcium oscillator ("membrane and Ca(2+)-clock"). The main feature of the model is a description of the stochastic dynamics of Ca2+ release units within the electron-conformational mechanism of the functioning of ryanodine-sensitive calcium channels. It is shown that interaction of two cellular oscillators provides a stable action potential generation in the cardiac pacemaker cells even in the case of the stochastic Ca2+ dynamics. We studied in detail the effect of ryanodine channels sensitivity to an increase in the intracellular calcium concentration in sarcoplasmic reticulum and in the dyadic space on the behavior of calcium-release system. A parametric analysis of the integrative model of pacemaker cells is performed.
