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.
Kimura
I
I
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Kondoh
T
T
Kimura
M
M
D000331:Aequorin / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003964:Diaphragm / Q000187:drug effects / Q000378:metabolism; D007202:Indicators and Reagents; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009119:Muscle Contraction / Q000187:drug effects; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D010791:Phrenic Nerve / Q000187:drug effects; D012132:Respiratory Muscles / Q000187:drug effects / Q000378:metabolism*
D007202:Indicators and Reagents; D009466:Neuromuscular Blocking Agents; D000331:Aequorin; D002118:Calcium