DIFFERENTIAL-EFFECTS OF GABA(A) RECEPTOR ANTAGONISTS IN THE CONTROL OF RESPIRATORY NEURONAL DISCHARGE PATTERNS

To ascertain the role of the inhibitory neurotransmitter gamma-aminobu tyric acid (GABA) in shaping and controlling the phasic discharge patt erns of medullary respiratory premotor neurons, localized pressure app lications of the competitive GABA(A) receptor antagonist bicuculline ( BIC) and the noncompetitive GABA(A) receptor antagonist picrotoxin (PI C) were studied. Multibarrel micropipettes were used in halothane anes thetized, paralyzed, ventilated, vagotomized dogs to record single uni t activity from inspiratory and expiratory neurons in the caudal ventr al respiratory group and to picoeject GABA(A) receptor antagonists. Th e moving time average of phrenic nerve activity was used to determine respiratory phase durations and to synchronize cycle-triggered histogr ams of discharge patterns. Picoejection of BIC and PIC had qualitative ly different effects on the discharge patterns of respiratory neurons. BIC caused an increase in the discharge rate during the neuron's acti ve phase without inducing activity during the neuron's normally silent phase. The resulting discharge patterns were amplified replicas (X2-3 ) of the underlying preejection phasic patterns. In contrast, picoejec tion of PIC did not increase the peak discharge rate during the neuron 's active phase but induced a tonic level of activity during the neuro n's normally silent phase. The maximum effective BIC dose (15 +/- 1.8 pmol/min) was considerably smaller than that for PIC (280 +/- 53 pmol/ min). These findings suggest that GABA(A) receptors with differential pharmacology mediate distinct functions within the same neuron, 1) gai n modulation that is BIC sensitive but PIC insensitive and 2) silent-p hase inhibition blocked by PIG. These studies also suggest that the ch oice of an antagonist is an important consideration in the determinati on of GABA receptor function within the respiratory motor control syst em.