Benzodiazepines and GABA-GABA_A receptor system in the cat carotid body

Benzodiazepines (BZs) suppress ventilation possibly by augmenting the GABA_a receptor activity in the respiratory control system, but precise sites of action are not well understood. The goals of this study were: (1) to identify GABA_a receptor subunits in the carotid body (CB) and petrosal ganglion (PG); (2) to test if BZs exert their effects through the GABA_a receptor in the CB chemosensory unit. Tissues were taken from euthanized adult cats. RNA was extracted from the brain, and cDNA sequences of several GABA_a receptor subunits were determined. Subsequent RT-PCR analysis demonstrated the gene expression of α2, α3, β3, and γ2 subunits in the CB and the PG. Immunoreactivity for GABA and for GABA_a receptor β3 and γ2 subunits was detected in chemosensory glomus cells (GCs) in the CB and neurons in the PG. The functional aspects of the GABA-GABA_a receptor system in the CB was studied by measuring CB neural output using in vitro perfusion setup. Two BZs, midazolam and diazepam, decreased the CB neural response to hypoxia. With continuous application of bicuculline, a GABA_a receptor antagonist, the effects of BZs were abolished. In conclusion, the GABA-GABA_a receptor system is functioning in the CB chemosensory system. BZs inhibit CB neural response to hypoxia by enhancing GABA_a receptor activity.