Modulation of the oligomerization of isolated ryanodine receptors by their functional states.
The calcium release channels/ryanodine receptors (RyRs) usually form two-dimensional regular lattices 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 [(3)H]ryanodine binding assay. High level of oligomerization is observed for resting closed RyR1s with nanomolar Ca(2+) in solution. Activation of RyR1s by micromolar Ca(2+) 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 Mg(2+). 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. These findings provide exciting new information to understand the function and operating mechanism of RyR arrays.
Hu
Xiao-Fang
XF
Bio-X Life Science Research Center, College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Liang
Xin
X
Chen
Ke-Ying
KY
Xie
Hong
H
Xu
Yuhong
Y
Zhu
Pei-Hong
PH
Hu
Jun
J
D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry; D002412:Cations; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015640:Ion Channel Gating; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism; D015233:Models, Statistical; D018482:Muscle, Skeletal / Q000378:metabolism; D017785:Photons; D011485:Protein Binding; D011487:Protein Conformation; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013053:Spectrophotometry
D015220:Calcium Channels; D002412:Cations; D019837:Ryanodine Receptor Calcium Release Channel; D000249:Adenosine Monophosphate; D008274:Magnesium; D002118:Calcium