Characterization of chloride efflux from GT1-7 neurons: Lack of effect of ethanol on GABA(A) response

Martin A Javors, Thomas S King, Xiaoying Chang, Maharaj K. Ticku, Charles Levinson

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The purpose of this study of GT1-7 neurons was to partially characterize basal Cl- transport and GABA(A) mediated Cl- efflux and to test the effect of ethanol on a GABA(A) receptor that lacks a γ subunit. We measured GABA(A) function and Cl- transport with 36C1-. Our results show that basel 36Cl- efflux varied with temperature at 4°C, 23°C, and 37°C. At 23°C, DIDS, an inhibitorof anion exchange, reduced basel 36Cl- efflux maximally by 79.6% with an IC50 of 42.1 μM, wheras burnetanide, an inhibitor of (Na-K-Cl) cotransport, had no effect on basal 36Cl- efflux at concentrations up to 150 μM. At 4°C, muscimol, a GABA(A) receptor agonist, stimulated 36Cl- efflux with an EC50 of 1.47 μM. Bicuculline, a GABA(A) receptor antagonist, completely reversed the effect of 20 μM muscimol with an IC50 of 6.08 μM. Ethanol, at concentrations up to 87 mM (0.4% (w/v)), had no effect on muscimol-induced 36Cl- efflux at 4°C or at 32°C. Our results indicate that stimulation of GABA(A) receptors causes an efflux of Cl- from GT1-7 neurons. This finding is consistent with the concept that stimulation of GABA(A) receptors produces depolarization of the plasma membrane, increase in cytosolic [Ca2+], and GnRH release. Our results represent the first description of chloride transport in GT1-7 neurons and suggest the presence of a Cl- exchange, but not (Na-K-Cl), transporter mechanism. Furthermore, the lack of an effect of ethanol observed in this study is consistent with the idea that a γ2L subunit may be necessary for the effects of low concentrations of ethanol at GABA(A) receptors.

Original languageEnglish (US)
Pages (from-to)183-189
Number of pages7
JournalBrain Research
Volume780
Issue number2
DOIs
StatePublished - Jan 12 1998

Fingerprint

GABA-A Receptors
Muscimol
gamma-Aminobutyric Acid
Chlorides
Ethanol
Neurons
Inhibitory Concentration 50
Sodium-Potassium-Chloride Symporters
GABA-A Receptor Agonists
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
GABA-A Receptor Antagonists
Bicuculline
Gonadotropin-Releasing Hormone
Anions
Cell Membrane
Temperature

Keywords

  • Chloride
  • Ethanol
  • GABA(A)
  • GnRH
  • GT1-7
  • Neuron

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Characterization of chloride efflux from GT1-7 neurons : Lack of effect of ethanol on GABA(A) response. / Javors, Martin A; King, Thomas S; Chang, Xiaoying; Ticku, Maharaj K.; Levinson, Charles.

In: Brain Research, Vol. 780, No. 2, 12.01.1998, p. 183-189.

Research output: Contribution to journalArticle

Javors, Martin A ; King, Thomas S ; Chang, Xiaoying ; Ticku, Maharaj K. ; Levinson, Charles. / Characterization of chloride efflux from GT1-7 neurons : Lack of effect of ethanol on GABA(A) response. In: Brain Research. 1998 ; Vol. 780, No. 2. pp. 183-189.
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