Influence of extracellular calcium and a water-soluble carboxyl group reagent on cholinergic drug-receptor interactions in skeletal muscle.

Contractions of frog rectus abdominus muscles induced by suxamethonium or decamethonium, and to a lesser extent by carbamylcholine, were decreased as the extracellular calcium concentration was increased. The inhibition of all three agonist responses by 1.1 mM calcium was competitive. The contractions induced by bis-onium compounds, but not carbamylcholine, were further antagonized at higher calcium concentrations (4.4 mM) in a noncompetitive manner. This latter effect of calcium may be due to antagonism of bis-onium compounds at a peripheral anionic site. Carboxyl group carbodiimide reagents inhibited muscle contractions, and this inhibition was slowly reversible. The extent of the inhibition was increased, and its recovery delayed, by prior exposure of the muscle to an agonist. The results support suggestions that receptor activation initially involves displacement of membrane calcium. The study provides further evidence that interaction of agonists iwth nicotinic receptors results in structural changes, possibly related to increased ion flow.