In vitro measurement of margin of safety of neuromuscular transmission.

The margin of safety of neuromuscular transmission was measured in isolated guinea pig lumbrical muscles. Twitch height of an indirectly stimulated muscle was reduced stepwise by suitable concentrations of tubocurarine for comparison with the associated occlusion of receptors by the drug. Receptor occlusion was estimated from the effect of tubocurarine on carbachol depolarization measured extracellularly by the moving-fluid electrode technique. Roughly 75-80% of the receptor pool had to be blocked before the twitch height began to fall, and 90-95% had to be blocked before the twitch response was completely abolished. These results agree well with those found previously in vivo. Thus, the present results add further support to the earlier measurements. In particular, artifacts that might have been present because of the complex pharmacokinetic situation in vivo have been ruled out.