Dynamic inter-receptor coupling: a novel working mechanism of 2-D ryanodine receptor array

¹ Shanghai Jiao Tong University

^* To whom correspondence should be addressed. E-mail: xfhu{at}sjtu.edu.cn.

Submitted on June 7, 2006
Revised on July 17, 2006
Accepted on 20 October 2006

	Abstract

Ryanodine receptors (RyRs) usually form 2-D regular array in sarcoplasmic reticulum (SR) membranes in muscle cells. The inter-RyRs coupling may be essential for the maintenance of quiescent Ca²⁺ release in resting state, as well as for the coordinated activation and rapid termination of RyR-mediated Ca²⁺ release during excitation-contraction coupling. In our previous work, we have reported that the inter-RyRs interaction is modulated by RyR channel's functional state, which inspired us to propose a novel working mechanism of RyR array: "dynamic inter-RyR coupling". In the present work, we built a simple model based on cellular automata and Monte-Carlo method to quantitatively investigate the roles of intermolecular coupling and its modulation in regulating the signaling capabilities of RyR array. Our simulation results showed that with a suitable inter-RyR coupling strength, the combination of rest stability and high response efficiency, namely optimal signal to noise ratio (SNR), of Ca²⁺ signaling could be achieved. Moreover, we also found the continued coupling between open RyRs would delay the system termination rate. The co-acquisition of robust termination of array opening relied on the proper decrease of coupling strength between activated RyRs. Obviously, such temporally asymmetric coupling would simultaneously endow the system with physiologically relevant resting stability and fast termination.

Key Words: dynamic coupling, rapid termination, resting stability, ryanodine receptor, two-dimensional array