Bicuculline, pentobarbital and diazepam modulate spontaneous GABA(A) channels in rat hippocampal neurons

Research output: Contribution to journalArticle

Abstract

Spontaneously opening, chloride-selective channels that showed outward rectification were recorded in ripped-off patches from rat cultured hippocampal neurons and in cell-attached patches from rat hippocampal CA1 pyramidal neurons in slices. In both preparations, channels had multiple conductance states and the most common single-channel conductance varied. In the outside-out patches it ranged from 12 to 70 pS (Vp=40 mV) whereas in the cell-attached patches it ranged from 56 to 85 pS (-Vp=80 mV). Application of GABA to a patch showing spontaneous channel activity evoked a rapid, synchronous activation of channels. During prolonged exposure to either 5 or 100 microM GABA, the open probability of channels decreased. Application of GABA appeared to have no immediate effect on single-channel conductance. Exposure of the patches to 100 microM bicuculline caused a gradual decrease on the single-channel conductance of the spontaneous channels. The time for complete inhibition to take place was slower in the outside-out than in the cell-attached patches. Application of 100 microM pentobarbital or 1 microM diazepam caused 2 - 4 fold increase in the maximum channel conductance of low conductance (<40 pS) spontaneously active channels. The observation of spontaneously opening GABA(A) channels in cell-attached patches on neurons in slices suggests that they may have a role in neurons in vivo and could be an important site of action for some drugs such as benzodiazepines, barbiturates and general anaesthetics.

Details

Authors
  • Bryndis Birnir
  • M Eghbali
  • A B Everitt
  • P W Gage
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Pharmacology and Toxicology

Keywords

  • current potentiation, gating, single channel conductance, GABAA receptors, anaesthetics, barbiturates, benzodiazepines, diazepam, bicuculline, inhibition
Original languageEnglish
Pages (from-to)695-704
JournalBritish Journal of Pharmacology
Volume131
Issue number4
Publication statusPublished - 2000
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: GABA Channels in Physiology and Pharmacology (013241570)