GABA(A) receptor heterogeneity in histaminergic neurons

Eur J Neurosci. 2002 Oct;16(8):1472-82. doi: 10.1046/j.1460-9568.2002.02221.x.

Abstract

Histaminergic neurons of the tuberomamillary nucleus display pacemaker properties; their firing rate is regulated according to behavioural state by gabaergic inhibition. Whole-cell recordings and single-cell RT-PCR from acutely isolated rat tuberomamillary neurons were used to characterize GABA -evoked currents and to correlate them with the expression pattern of 12 GABAA receptor subunits. We report differences in sensitivity to GABA and zinc as well as in the modulation of IPSC-decay times by zolpidem in histaminergic neurons expressing gamma-subunits at different levels. Immunocytochemistry and pharmacological analysis of whole-cell GABA-currents in these neurons revealed that all carry the gamma2-subunit protein and that all receptors contain at least one gamma-subunit. Neurons with different expression levels of gamma-subunits displayed a difference in cooperativity of GABA and zolpidem binding which we explain by the presence of one vs. two gamma-subunits in one receptor. Thus, we describe here native GABAA receptor function in relation to its stoichiometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Clocks / drug effects
  • Biological Clocks / genetics
  • Dose-Response Relationship, Drug
  • Drug Interactions / physiology
  • GABA Agonists / pharmacology
  • Histamine / metabolism*
  • Hypothalamic Area, Lateral / cytology
  • Hypothalamic Area, Lateral / drug effects
  • Hypothalamic Area, Lateral / metabolism*
  • Immunohistochemistry
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Pyridines / pharmacology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism*
  • Sleep / drug effects
  • Sleep / genetics
  • Zolpidem
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • GABA Agonists
  • Pyridines
  • RNA, Messenger
  • Receptors, GABA-A
  • gamma-Aminobutyric Acid
  • Zolpidem
  • Histamine