The effect of age on the safety factor in neuromuscular transmission in the isolated diaphragm of the rat.
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 in neonates.