Effects of neuromuscular blocking agents on central respiratory control in the isolated brainstem–spinal cord of neonatal rat

Although neuromuscular blocking agents (NMBAs) function as muscular nicotinic acetylcholine receptor (nAChR) antagonists, several studies have shown that they block neuronal nAChRs as well, which led us to hypothesize that these agents can affect neuronal nAChRs expressed in respiratory centers. To test this hypothesis, we studied the effects of two NMBAs on respiratory activity and respiratory neurons in brainstem-spinal cord preparations from neonatal rats. The application of either D-tubocurarine or vecuronium resulted in dose-dependent reductions in C4 respiratory rate. These reductions were concomitant with reductions in the depolarizing cycle rate of inspiratory (Insp) neurons; the depolarizing cycle rate of preinspiratory (Pre-I) neurons, however, was not affected. We also detected C4 burst activity during the depolarizing phase in Pre-I neurons, even during NMBA-induced respiratory depression. Both NMBAs inhibited drive potential amplitude and intraburst firing frequency in Insp and Pre-I neurons. These agents also induced a hyperpolarization and an increase in membrane resistance in Pre-I neurons, however they had no effect on these membrane properties in Insp neurons. Our findings indicate that these agents suppress central respiratory activity mainly through their inhibitory effects on Pre-I neurons and the Pre-I to Insp neuron synaptic drive, and that nAChRs are involved in central respiratory control.