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

A. Igarashi, N. Zadzilka, M. Shirahata

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Benzodiazepines (BZs) suppress ventilation possibly by augmenting the GABAa 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 GABAa receptor subunits in the carotid body (CB) and petrosal ganglion (PG); (2) to test if BZs exert their effects through the GABAa receptor in the CB chemosensory unit. Tissues were taken from euthanized adult cats. RNA was extracted from the brain, and cDNA sequences of several GABAa 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 GABAa 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-GABAa 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 GABAa receptor antagonist, the effects of BZs were abolished. In conclusion, the GABA-GABAa receptor system is functioning in the CB chemosensory system. BZs inhibit CB neural response to hypoxia by enhancing GABAa receptor activity.

Original languageEnglish (US)
Title of host publicationArterial Chemoreceptors
EditorsConstancio Gonzalez, Colin Nurse, Chris Peers
Pages169-175
Number of pages7
DOIs
StatePublished - 2009

Publication series

NameAdvances in Experimental Medicine and Biology
Volume648
ISSN (Print)0065-2598

Keywords

  • Benzodiazepine
  • Bicuculline
  • Carotid body
  • Diazepam
  • GABA
  • GABA receptor
  • Hypoxia
  • Immunohistochemistry
  • RT-PCR

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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