Effect of gallopamil on excitation-contraction coupling

1. Investigations performed in skeletal muscle have suggested that phenylalkylamine calcium antagonists, particularly gallopamil, affect excitation-contraction coupling independently of their effect on the sarcolemmal calcium current. 2. Sarcoplasmic reticulum and single channel studies have provided evidence that phenylalkylamine calcium antagonists inhibit calcium release through the sarcoplasmic reticulum calcium channel/ryanodine receptor. This action has not been observed with dihydropyridine calcium antagonists. 3. Binding experiments have confirmed the existence of intracellular binding sites for phenylalkylamines, and have shown that gallopamil interferes with the binding of ryanodine to its low affinity sites. 4. The dose-response relationship for the effect of gallopamil on excitation-contraction coupling has not been definitely established. However, there is evidence that gallopamil may be effective at concentrations that are close to the therapeutic range.