Format

Send to

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

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

Author information

1
Department of Neuroscience, Uppsala University, Uppsala, Sweden.
2
Department of Immunology, Genetic and Pathology, and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
3
Department of Neuroscience, Uppsala University, Uppsala, Sweden. Electronic address: bryndis.birnir@neuro.uu.se.

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

PMID:
25510230
DOI:
10.1016/j.ejphar.2014.12.001
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center