The Journal of Neurophysiology Vol. 80 No. 5 November 1998, pp. 2368-2377
Copyright ©1998 The American Physiological Society

Differential Effects of GABA_A Receptor Antagonists in the Control of Respiratory Neuronal Discharge Patterns

Z. Dogas^{1, 2}, M. Krolo^{1, 2}, E. A. Stuth^{1, 2}, M. Tonkovic-Capin^{1, 2}, F. A. Hopp^{1, 2}, D. R. McCrimmon³, and E. J. Zuperku^{1, 2}

¹ Zablocki Veterans Affairs Medical Center; and ² Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53295; and ³ Department of Physiology and Institute for Neuroscience, Northwestern University Medical School, Chicago, Illinois 60611

Dogas, Z., M. Krolo, E. A. Stuth, M. Tonkovic-Capin, F. A. Hopp, D. R. McCrimmon, and E. J. Zuperku. Differential effects of GABA_A receptor antagonists in the control of respiratory neuronal discharge patterns. J. Neurophysiol. 80: 2368-2377, 1998. To ascertain the role of the inhibitory neurotransmitter -aminobutyric acid (GABA) in shaping and controlling the phasic discharge patterns of medullary respiratory premotor neurons, localized pressure applications of the competitive GABA_A receptor antagonist bicuculline (BIC) and the noncompetitive GABA_A receptor antagonist picrotoxin (PIC) were studied. Multibarrel micropipettes were used in halothane anesthetized, paralyzed, ventilated, vagotomized dogs to record single unit activity from inspiratory and expiratory neurons in the caudal ventral respiratory group and to picoeject GABA_A receptor antagonists. The moving time average of phrenic nerve activity was used to determine respiratory phase durations and to synchronize cycle-triggered histograms of discharge patterns. Picoejection of BIC and PIC had qualitatively different effects on the discharge patterns of respiratory neurons. BIC caused an increase in the discharge rate during the neuron's active phase without inducing activity during the neuron's normally silent phase. The resulting discharge patterns were amplified replicas (×2-3) of the underlying preejection phasic patterns. In contrast, picoejection of PIC did not increase the peak discharge rate during the neuron's active phase but induced a tonic level of activity during the neuron'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) gain modulation that is BIC sensitive but PIC insensitive and 2) silent-phase inhibition blocked by PIC. These studies also suggest that the choice of an antagonist is an important consideration in the determination of GABA receptor function within the respiratory motor control system.

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