EFFECT OF GALLOPAMIL ON EXCITATION-CONTRACTION COUPLING

1. Investigations performed in skeletal muscle have suggested that phe nylalkylamine calcium antagonists, particularly gallopamil, affect exc itation-contraction coupling independently of their effect on the sarc olemmal calcium current.2. Sarcoplasmic reticulum and single channel s tudies have provided evidence that phenylalkylamine calcium antagonist s inhibit calcium release through the sarcoplasmic reticulum calcium c hannel/ryanodine receptor. This action has not been observed with dihy dropyridine calcium antagonists. 3. Binding experiments have confirmed the existence of intracellular binding sites for phenylalkylamines, a nd 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 d efinitely established. However, there is evidence that gallopamil may be effective at concentrations that are close to the therapeutic range .