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

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 36μM. The currents were activated by THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and enhanced by the benzodiazepine diazepam (1μM) and the general anesthetics etomidate and propofol (50μM). In line with the expressed GABAA receptors containing at least the α3β3θ subunits, the receptors were highly sensitive to etomidate (EC50=55nM). 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.

Jin, ZheUppsala universitet,Fysiologi(Swepub:uu)zheji315 (author)
Bhandage, Amol K.,1988-Uppsala universitet,Fysiologi,Bryndis Birnir(Swepub:uu)amebh673 (author)
Korol, Sergiy VUppsala universitet,Fysiologi(Swepub:uu)serko922 (author)
Westermark, BengtUppsala universitet,Cancer och vaskulärbiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)bengtwm (author)
Forsberg Nilsson, KarinUppsala universitet,Cancer och vaskulärbiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)karifors (author)
Uhrbom, LeneUppsala universitet,Science for Life Laboratory, SciLifeLab,Cancer och vaskulärbiologi(Swepub:uu)leneuhrb (author)
Smits, AnjaUppsala universitet,Neurologi(Swepub:uu)anjasmit (author)
Birnir, BryndisUppsala universitet,Neurologi(Swepub:uu)brybi979 (author)
Uppsala universitetFysiologi (creator_code:org_t)

In:European Journal of Pharmacology: Elsevier BV748, s. 101-1070014-29991879-0712

By the author/editor: Babateen, Omar; Jin, Zhe; Bhandage, Amol K ...; Korol, Sergiy V; Westermark, Beng ...; Forsberg Nilsson ...; show more...; Uhrbom, Lene; Smits, Anja; Birnir, Bryndis; show less...

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