Ryanoid modification of the cardiac muscle ryanodine receptor channel results in relocation of the tetraethylammonium binding site

The Journal of General Physiology
Bhavna TannaA J Williams

Abstract

The interaction of ryanodine and derivatives of ryanodine with the high affinity binding site on the ryanodine receptor (RyR) channel brings about a characteristic modification of channel function. In all cases, channel open probability increases dramatically and single-channel current amplitude is reduced. The amplitude of the ryanoid-modified conductance state is determined by structural features of the ligand. An investigation of ion handling in the ryanodine-modified conductance state has established that reduced conductance results from changes in both the affinity of the channel for permeant ions and the relative permeability of ions within the channel (Lindsay, A.R.G., A. Tinker, and A.J. Williams. 1994. J. Gen. Physiol. 104:425-447). It has been proposed that these alterations result from a reorganization of channel structure induced by the binding of the ryanoid. The experiments reported here provide direct evidence for ryanoid-induced restructuring of RyR. TEA+ is a concentration- and voltage-dependent blocker of RyR in the absence of ryanoids. We have investigated block of K+ current by TEA+ in the unmodified open state and modified conductance states of RyR induced by 21-amino-9alpha-hydroxyryanodine, 21-azido-9alph...Continue Reading

References

Sep 1, 1987·The American Journal of Physiology·E RousseauG Meissner
Jun 1, 1973·The Journal of General Physiology·A M Woodhull
Dec 1, 1982·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·C Miller
Sep 1, 1994·The Journal of General Physiology·A R LindsayA J Williams
Apr 1, 1994·British Journal of Pharmacology·S J McGarry, A J Williams

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Citations

Apr 27, 2010·Pflügers Archiv : European journal of physiology·Josefina Ramos-FrancoMichael Fill
May 24, 2007·Molecular Membrane Biology·Kishani M RanatungaAlan J Williams
Mar 28, 2002·Biophysical Journal·Fiona Mead, Alan J Williams
Apr 19, 2002·The Journal of Pharmacology and Experimental Therapeutics·Robert G TsushimaJ Andrew Wasserstrom

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