Jan 18, 2005

Voltage-sensitive equilibrium between two states within a ryanoid-modified conductance state of the ryanodine receptor channel

Biophysical Journal
Bhavna TannaAlan J Williams

Abstract

We have investigated the influence of transmembrane holding potential on the kinetics of interaction of a cationic ryanoid, 8beta-amino-9alpha-hydroxyryanodine, with individual ryanodine receptor (RyR) channels and on the functional consequences of this interaction. In agreement with previous studies involving cationic, neutral, and anionic ryanoids, both rates of association and dissociation of the ligand are sensitive to transmembrane potential. A voltage-sensitive equilibrium between high- and low-affinity forms of the receptor underlies alterations in rates of association and dissociation of the ryanoid. The interaction of 8beta-amino-9alpha-hydroxyryanodine with RyR influences the rate of cation translocation through the channel. With this ryanoid bound, the channel fluctuates between two clearly resolved subconductance states (alpha and beta). We interpret this observation as indicating that with 8beta-amino-9alpha-hydroxyryanodine bound, the pore of the RyR channel exists in two essentially isoenergetic conformations with differing ion-handling properties. The equilibrium between the alpha- and beta-states of the RyR-8beta-amino-9alpha-hydroxyryanodine complex is sensitive to transmembrane potential. However, the mechani...Continue Reading

Mentioned in this Paper

Fluctuation
8beta-amino-9alpha-hydroxyryanodine
Ryanodine Receptor 3
Calcium
Protoplasm
Resting Potentials
RYR2 gene
Ions
Dall Sheep
Myocardium

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