Faculty Collaboration Database

Differential effects of GABAA receptor antagonists in the control of respiratory neuronal discharge patterns. J Neurophysiol 1998 Nov;80(5):2368-77

Date

11/18/1998

Pubmed ID

9819249

DOI

10.1152/jn.1998.80.5.2368

Scopus ID

2-s2.0-0031597393 (requires institutional sign-in at Scopus site)   56 Citations

Abstract

To ascertain the role of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in shaping and controlling the phasic discharge patterns of medullary respiratory premotor neurons, localized pressure applications of the competitive GABAA receptor antagonist bicuculline (BIC) and the noncompetitive GABAA 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 GABAA 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 (x2-3) 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 GABAA 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.

Author List

Dogas Z, Krolo M, Stuth EA, Tonkovic-Capin M, Hopp FA, McCrimmon DR, Zuperku EJ

Authors

Eckehard A. Stuth MD Professor in the Anesthesiology department at Medical College of Wisconsin
Edward J. Zuperku PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Bicuculline
Dogs
Drug Antagonism
Electrophysiology
Female
GABA Antagonists
Male
Medulla Oblongata
Motor Neurons
Periodicity
Picrotoxin
Receptors, GABA-A
Respiratory Mechanics
Spinal Cord
Stereotaxic Techniques
gamma-Aminobutyric Acid