Age-dependent variation in response to tubocurarine in the isolated rat diaphragm

The EC50 of tubocurarine was determined in phrenic nerve-hemidiaphragm preparations obtained from 35 Sprague-Dawley rats aged 0-46 days. We measured also the ratio of the fourth to the first twitch in the train-of-four (T4:T1) when the first twitch of the train was depressed to 50% of control. The preparation was not unduly sensitive to tubocurarine at 0 days and there was little evidence of T4:T1 fade. However, by age 11 days the preparation exhibited fade and a three-fold sensitivity to tubocurarine similar to that in the human neonate. We conclude that the phrenic nerve-hemidiaphragm preparation from 11-day-old rats should be a suitable model in which to investigate the biochemical and electrophysiological basis of the sensitivity seen in humans.