Effects of ryanodine on inotropic and arrhythmogenic actions of cardiotonic steroids

In addition to its role in myocardial excitation-contraction coupling, the sarcoplasmic reticulum may be involved in arrhythmogenic actions of cardiotonic steroids. This study in isolated cardiac muscle demonstrates that ryanodine can prevent the arrhythmias and reduce the positive inotropic effect produced by cardiotonic steroids without affecting their specific binding to sites on Na,K-ATPase. These data suggest that the antagonism is mediated by ryanodine-induced alterations in Ca2+ release from the sarcoplasmic reticulum.