Etomidate, propofol and diazepam potentiate GABA-evoked GABAA currents in a cell line derived from human glioblastoma

Eur J Pharmacol. 2015 Feb 5;748:101-7. doi: 10.1016/j.ejphar.2014.12.001. Epub 2014 Dec 12.

Abstract

GABAA receptors are pentameric chloride ion channels that are opened by GABA. We have screened a cell line derived from human glioblastoma, U3047MG, for expression of GABAA receptor subunit isoforms and formation of functional ion channels. We identified GABAA receptors subunit α2, α3, α5, β1, β2, β3, δ, γ3, π, and θ mRNAs in the U3047MG cell line. Whole-cell GABA-activated currents were recorded and the half-maximal concentration (EC₅₀) for the GABA-activated current was 36 μM. The currents were activated by THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and enhanced by the benzodiazepine diazepam (1 μM) and the general anesthetics etomidate and propofol (50 μM). In line with the expressed GABAA receptors containing at least the α3β3θ subunits, the receptors were highly sensitive to etomidate (EC₅₀=55 nM). Immunocytochemistry identified expression of the α3 and β3 subunit proteins. Our results show that the GABAA receptors in the glial cell line are functional and are modulated by classical GABAA receptor drugs. We propose that the U3047MG cell line may be used as a model system to study GABAA receptors function and pharmacology in glial cells.

Keywords: Anesthetics; Benzodiazepine; GABA agents; GABA(A) receptors; Glioma; Whole-cell recordings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, General / pharmacology*
  • Cell Line, Tumor
  • Diazepam / pharmacology*
  • Drug Synergism
  • Electrophysiological Phenomena / drug effects*
  • Etomidate / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioblastoma / pathology*
  • Humans
  • Ion Channel Gating / drug effects
  • Isoxazoles / pharmacology*
  • Propofol / pharmacology
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Protein Transport / drug effects
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism*
  • gamma-Aminobutyric Acid / pharmacology*

Substances

  • Anesthetics, General
  • Isoxazoles
  • Protein Subunits
  • Receptors, GABA-A
  • gamma-Aminobutyric Acid
  • gaboxadol
  • Diazepam
  • Propofol
  • Etomidate