Electron-conformational transformations govern the temperature dependence of the cardiac ryanodine receptor gating

Abstract

Temperature influences many aspects of cardiac excitation-contraction coupling, in particular, hypothermia increases the open probability (Popen) 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 Popen and mean open time without any significant effect on mean closed