Z. Dogas et al., DIFFERENTIAL-EFFECTS OF GABA(A) RECEPTOR ANTAGONISTS IN THE CONTROL OF RESPIRATORY NEURONAL DISCHARGE PATTERNS, Journal of neurophysiology, 80(5), 1998, pp. 2368-2377
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.