Low quantal content of the endplate potential reduces safety factor for neuromuscular transmission in the diaphragm of the newborn rat

Abstract

We have used phrenic nerve-hemidiaphragm preparations from rats aged 11-28 days to determine the electrophysiological basis of the three-fold increase in sensitivity of the neonatal neuromuscular junction to non-depolarizing neuromuscular blocking drugs. The mean resting membrane potential (RMP) of intact muscle fibres at 19-21 degrees C increased from -67.1 (SEM 0.6) mV at 11 days to -75.8 (0.06) mV at 28 days. Over the same age range the mean size of miniature endplate potentials (MEPP) decreased from 1.7 (0.1) mV to 1.4 (0.03) mV, and the threshold depolarization to produce a muscle action potential increased from 6.8 (0.4) mV to 9.5 (0.6) mV. The quantal content of the evoked endplate potential (EPP) calculated from EPP and MEPP measured in cut muscle fibres was only 6.6 (0.9) at 11 days, but this increased to 21.1 (2.3) at 21 days. As a result of the low quantal content of the EPP, the safety factor for neuromuscular transmission was only 1.7 at 11 days, compared with 2.8 at 20 days. A safety factor of 1.7 in the youngest rats indicates that block of only about 40% of postjunctional acetylcholine receptors would result in failure of neuromuscular transmission. Hence, a low quantal content of EPP, leading to a low safety factor for neuromuscular transmission, probably underlies the increased sensitivity to non-depolarizing neuromuscular blocking drugs of young rats and, by inference, human neonates.