Effects of halothane on synaptic neurotransmission to medullary expiratoryneurons in the ventral respiratory group of dogs

Background: The activity of canine expiratory neurons is primarily dependen t on N-methyl-D-aspartic acid (NMDA)-receptor mediated excitatory chemodriv e inputs and a powerful inhibitory gain modulatory mechanism mediated via g amma-aminobutyric acid(A) (GABA(A)) receptors. We examined whether the depr essant effect of halothane on expiratory neuronal activity is primarily cau sed by a reduction in glutamatergic excitation or a potentiation of the inh ibitory mechanism. Methods: Experiments were performed in halothane-anesthetized, vagotomized, paralyzed, and mechanically ventilated dogs during hypercapnic hyperoxia. The effect of a halothane dose increase from one minimum alveolar concentra tion (MAC) to 2 MAC on extracellularly recorded expiratory neuronal activit y was studied before and during complete GABA(A) receptor blockade by local ized picoejection of bicuculline close to the neuron. Complete blockade of the inhibitory mechanism allowed differentiation between the effects of hal othane on overall NMDA-mediated excitation and on GABA(A)-mediated inhibiti on. Results: The spontaneous activity of 12 expiratory neurons was significantl y depressed (18.1%) by the 1-MAC halothane dose increase. Overall glutamate rgic excitation was depressed 38.3 +/- 12.3% (mean +/- SD) by the 1-MAC hal othane increase. The prevailing GABA(A) ergic attenuation of neuronal outpu t decreased significantly from 49.5 +/- 10 to 32.0 +/- 10.4%. Thus overall inhibition was reduced by halothane by 33.5 +/- 17.2%. Conclusions: These results suggest that the depressive effect of a 1-MAC ha lothane dose increase on expiratory neuronal activity in our in vivo prepar ation with an intact neural network was mainly caused by a reduction of syn aptic excitatory mechanisms and not an enhancement of synaptic inhibitory m echanisms.