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An analysis of neuromuscular transmission has been made in phrenic nerve/diaphragm preparations from male rats aged 30 days or 110 days. The amplitude of miniature end-plate potentials was found to decrease with age, being 0.969±SEM 0.058 mV at 30 days and 0.510±SEM 0.031 mV at 110 days. Over the same period, the quantum content of the first end-plate potential of a train of 40 at 10 Hz, increased from 144.5, SEM+11.1, −10.4 to 346, SEM+41.4, −37.0. A corresponding change was observed also in the average quantum contents of the last 30 end-plate potentials of each train; from 50.6, SEM+ 3.5, −3.2, to 138.9, SEM+15.0, −13.6. The safety factor for neuromuscular transmission, calculated from these measured parameters, was found at 30 days to be only 70–80% of that at 110 days. It was estimated that the lower safety factor found in young rats was approximately equivalent to the neuromuscular blocking action of a dose of, at least, 0.0225 mg/kg of d-tubocurarine. Extrapolation of these results to man would support previous reports of increased sensitivity to d-tubocurarine inneonates.

In order to evaluate the sensitivity of different muscle types to neuromuscular blocking drugs, a system using mouse muscles in vitro was developed and applied to detect changes in drug sensitivity in relation to age. The effect of pancuronium and tubocurarine on initial twitch and on the ratio of fourth twitch to first twitch (T4/T1) of a train-of-four at 2 Hz were compared in fast-twitch, slow-twitch and respiratory muscles in the mouse. The muscles used were: extensor digitorum longus (EDL), soleus (SOL) and diaphragm (DIA). For both drugs the order of decreasing sensitivity was EDL > SOL > DIA. This result was the same whether first twitch or T4/T1 was used, although the latter was a more sensitive indicator. The sensitivity of neuromuscular block was less in muscles from old (30–33 month) animals than in the equivalent muscles from young (8–12 month) animals.