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Biophys. J. BioFAST: First Published June 10, 2005. doi:10.1529/biophysj.105.065409
© 2005 by the Biophysical Society.


A more recent version of this article appeared on September 1, 2005.
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CHANNELS, RECEPTORS, AND ELECTRICAL SIGNALING

Modulation of the oligomerization of isolated ryanodine receptors by their functional states

Xiaofang Hu 1, Xin Liang 1, Keying Chen 1, Hong Xie 2, Yuhong Xu 3, Peihong Zhu 2 and Jun Hu 1*

1 Bio-X Life Science Research Center, Shanghai Jiao Tong University
2 Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Scie
3 School of Pharmacy, Shanghai Jiao Tong University

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

Submitted on April 26, 2005
Revised on May 25, 2005
Accepted on 27 May 2005


   Abstract
The calcium release channels/ryanodine receptors (RyRs) usually form 2-D regular lattice in the endoplasmic/sarcoplasmic reticulum membranes. However, the function and modulation of the interaction between neighboring RyRs are still unknown. Here, with an in vitro aqueous system, we demonstrate that the interaction between RyRs isolated from skeletal muscle (RyR1s) is modulated by their functional states by using photon correlation spectroscopy and [3H]ryanodine binding assay. High level of oligomerization is observed for resting closed RyR1s with nanomolar Ca2+ in solution. Activation of RyR1s by micromolar Ca2+ or/and millimolar AMP leads to the de-oligomerization of RyR1s. The oligomerization of RyR1s remains at high level when RyR1s are stabilized at closed state by Mg2+. The modulation of RyR1-RyR1 interaction by the functional state is also observed under near physiological conditions, suggesting that the interaction between arrayed RyR1s would be dynamically modulated during excitation-contraction coupling (E-C coupling). These findings provide exciting new information to understand the function and operating mechanism of RyR arrays.

Key Words: excitation-contraction coupling, functional states, interaction, modulation, oligomerization/de-oligomerization, photon correlation spectroscopy




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Copyright © 2005 by the Biophysical Society.