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

Br J Pharmacol. 2000 Oct;131(4):695-704. doi: 10.1038/sj.bjp.0703621.

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.

MeSH terms

  • Animals
  • Bicuculline / pharmacology*
  • Cells, Cultured
  • Diazepam / pharmacology*
  • GABA Modulators / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • Ion Channels / drug effects*
  • Pentobarbital / pharmacology*
  • Rats
  • Receptors, GABA-A / drug effects*
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • GABA Modulators
  • Ion Channels
  • Receptors, GABA-A
  • gamma-Aminobutyric Acid
  • Pentobarbital
  • Diazepam
  • Bicuculline