The Electron-Conformational Model of Ryanodine Receptors of the Heart Cell

Abstract

The main ideas of an electron-conformational (EC) model of ligand-activated ryanodine channels (RyR) that reduces many degrees of freedom of this gigantic nanoscopic molecular complex to two so-called electron and conformational degrees of freedom are presented. In the toy model, the conformational potential or energy profile of the RyR channel represents two branches that describe the dependence of energy on the conformational coordinate (reaction coordinate) in the initial and ligand-activated states, respectively. A model extension that takes into account both the tetrameric structure of the RyR channel and additional (orthogonal) rotational conformational mode has been considered. The EC model has been demonstrated to give a biophysical basis to the traditional phenomenological model of Markov chains. To demonstrate the possibilities of the EC model, we refer to examples of model description of the dynamics of isolated RyR channels and clusters of RyR channels in release units of the heart cell.