Changes in intracellular Ca2+ produced in the mouse diaphragm by neuromuscular blocking drugs

Differences between the effects of depolarizing and competitive neuromuscular blocking drugs on Ca2(+)-aequorin luminescences (Ca2+ transients) emitted during twitches were compared in indirectly-stimulated diaphragm muscles of mice. Succinylcholine enhanced intracellular Ca2+ transients at concentrations of 1.3-2.5 microM and inhibited them at concentrations of 5.0-50 microM, demonstrating a biphasic response as in the case of twitch tensions. However, the response to Ca2+ transients was two to three times more sensitive than the response to twitch tension. Decamethonium 2.4-96 microM and carbachol 5.5-109 microM produced similar results. In contrast, pancuronium and (+)-tubocurarine inhibited them in the same concentration ranges. The relation between Ca2+ transients and twitch tensions was hyperbolic and was computer-simulated by the Hill equation in the case of succinylcholine, decamethonium and carbachol, whereas it was represented by a single exponential equation in the case of pancuronium, (+)-tubocurarine, and submaximal nerve-stimulation voltage. Spontaneous Ca2+ transients, on the other hand, were generated only in response to depolarizing drugs at concentrations having a neuromuscular blocking effect. These results suggest that depolarizing and competitive neuromuscular blocking drugs affect intracellular Ca2+ mobilization by different routes mediated by acetylcholine receptors.