Kimura I, Kondoh T, Kimura M
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
J Pharm Pharmacol. 1990 Sep;42(9):626-31. doi: 10.1111/j.2042-7158.1990.tb06620.x.
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.
在小鼠间接刺激的膈肌中，比较了去极化和竞争性神经肌肉阻滞药物对抽搐期间发射的Ca2(+)-水母发光蛋白发光（Ca2+瞬变）的影响差异。琥珀酰胆碱在1.3 - 2.5 microM浓度下增强细胞内Ca2+瞬变，在5.0 - 50 microM浓度下抑制它们，如在抽搐张力情况下一样表现出双相反应。然而，对Ca2+瞬变的反应比对抽搐张力的反应敏感两到三倍。2.4 - 96 microM的十烃季铵和5.5 - 109 microM的卡巴胆碱产生了类似的结果。相比之下，泮库溴铵和(+)-筒箭毒碱在相同浓度范围内抑制它们。Ca2+瞬变与抽搐张力之间的关系是双曲线的，在琥珀酰胆碱、十烃季铵和卡巴胆碱的情况下由希尔方程进行计算机模拟，而在泮库溴铵、(+)-筒箭毒碱和次最大神经刺激电压的情况下由单指数方程表示。另一方面，仅在对具有神经肌肉阻滞作用浓度的去极化药物有反应时才产生自发Ca2+瞬变。这些结果表明，去极化和竞争性神经肌肉阻滞药物通过乙酰胆碱受体介导的不同途径影响细胞内Ca2+动员。
