Gold ion inhibits silver ion induced contracture and activates ryanodine receptors in skeletal muscle

Abstract

Effects of Au3+ on Ag(+)-induced contractures and Ca2+ release channel activity in the sarcoplasmic reticulum were studied in frog skeletal muscles. Single fibres spontaneously produced phasic and tonic contractures upon addition of 5-20 microM Ag+ or more than 50 microM Au3+. Simultaneous application of 5 microM Ag+ and 20 microM Au3+ inhibited contractures induced by Ag+. Au3+ applied immediately after development of Ag(+)-induced contractures shortened the duration of the phasic contracture and markedly decreased the subsequent tonic contracture. Pretreatment of fibres with Au3+ inhibited the Ag(+)-induced phasic contracture. Ca2+ release channels incorporated into planar lipid bilayers were activated in response to Au3+ at 20 to 200 microM. A close relationship was observed between Ca2+ release channel open probability and amplitude of the Au(3+)-induced tonic contracture. Channel activity was inhibited by 5 microM ruthenium red. We conclude that extracellular Au3+ at low concentrations modifies the interaction of Ag+ with voltage sensors in the transverse tubules to inhibit the Ag(+)-induced contracture and, if it enters the cell, Au3+ may directly activate the sarcoplasmic reticulum Ca2+ release channel to partially contribute to the tonic contracture.