Electron-conformational model of ryanodine receptor lattice dynamics
- 作者：A.S. Moskvin ; M.P. Philipiev ; O.E. Solovyova ; P. Kohl and V.S. Markhasin
- 关键词：Calcium-induced calcium release ; Ryanodine receptor/channel ; Electron-conformational coupling ; Auto-oscillation
- 刊名：Progress in Biophysics and Molecular Biology
- 出版年：2006
- 期刊代码：131_00796107
- 类别：bio
- 出版时间：January-April 2006
- 卷：90
- 期：1-3
- 页码：88-103
- 文件大小：558 K
摘要
We propose a simple, physically reasonable electron–conformational model for the ryanodine receptor (RyR) and, on that basis, present a theory to describe RyR lattice responses to L-type channel triggering as an induced non-equilibrium phase transition. Each RyR is modelled with a single open and a single closed (electronic) state only, described utilizing a e="mml4"> pseudospin approach. In addition to the fast electronic degree of freedom, the RyR channel is characterized by a slow classical conformational coordinate, Q, which specifies the RyR channel calcium conductance and provides a multimodal continuum of possible RyR states. The cooperativity in the RyR lattice is assumed to be determined by inter-channel conformational coupling. Given a threshold sarcoplasmic reticulum (SR) calcium load, the RyR lattice fires due to a nucleation process with a step-by-step domino-like opening of a fraction of lattice channels, providing for a sufficient release to generate calcium sparks. The optimal mode of RyR lattice functioning during calcium-induced calcium release implies a fractional release with a robust termination due to a decrease in SR calcium load, accompanied by a respective change in effective conformational strain of the lattice. SR calcium overload is shown to result in excitation of RyR lattice auto-oscillations with spontaneous RyR channel opening and closure.