Temperature influences many aspects of cardiac excitation-contraction coupling, in particular, hypothermia increases the open probability (P_open) of cardiac sarcoplasmic reticulum (SR) Ca²⁺-release channels (ryanodine-sensitive RyR channels) rising the SR Ca²⁺ load in mammalian myocytes. However, to the best of our knowledge, no theoretical models are available for that effect. Traditional Markov chain models do not provide a reasonable molecular mechanistic insight on the origin of the temperature effects. Here in the paper we address a simple physically clear electron-conformational model to describe the RyR gating and argue that a synergetic effect of external thermal fluctuation forces (Gaussian–Markovian noise) and internal friction via the temperature stimulation/suppression of the open–close RyR tunneling probability can be considered as a main contributor to temperature effects on the RyR gating. Results of the computer modeling allowed us to successfully reproduce all the temperature effects observed for an isolated RyR gating in vitro under reducing the temperature: increase in P_open and mean open time without any significant effect on mean closed

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 Ca²⁺ clock”) into account. The main feature of the model is a description of the stochastic dynamics of Ca²⁺ 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 Ca²⁺ 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.