ETHANOL AND GABA A RECEPTOR FUNCTION IN GT1-7 NEURONS

Project: Research project

Project Details

Description

GT1-7 hypothalamic neurons, which synthesize and secrete gonadotropin
releasing hormone (GnRH), have recently been developed and immortalized
from transgenic mice and are the only cell line to express GABA(A)
receptors. Stimulation of GABA(A) receptors in GT1-7 neurons results in
membrane depolarization, not hyperpolarization, a unique function
characteristic of these cells. Our preliminary experiments, as well as
other recent reports, showed that muscimol, a GABA(A) agonist, stimulated
C1- efflux, increased cytosolic [Ca2+), and stimulated GnRH release in
GT1-7 cells. These effects were inhibited by bicuculline, a GABA(A)
antagonist, and nimodipine, an L-type Ca2+ channel antagonist. Ethanol
(50 mM) enhanced muscimol-induced GABA(A) function despite the fact that
the GABA(A) receptors in these cells do not appear to contain a gamma
subunit. Therefore, we hypothesize that acute ethanol exposure affects
GABA(A) receptor function in a novel way that may include enhancement of
chloride efflux and calcium ion conductance. To test our hypothesis, we
propose the following specific aims: Specific Aim 1. Characterize the basic function characteristics of the
GABA(A) receptor system in GT1-7 neurons. We will characterize GABA(A)
mediated increase in [Ca2+]cyt, C1- efflux, membrane potential changes,
and GnRH release in GT1-7 cells using muscimol as a GABA(A) agonist and
bicuculline as a GABA(A) antagonist. We will determine the involvement
of L-type Ca2+ channels in GABA(A) mediated increase in [Ca2+]cyt using
nimodipine (an L-type Ca2+ channel antagonist) and BayK 8644 )an L-type
Ca2+ channel agonist). Specific Aim 2. Characterize the acute effects of ethanol on GABA(A)
function in GT1-7 cells. We will characterize the effects of acute
ethanol treatment on GABA(A) mediated increase in [Ca2+]cyt, C1- efflux,
membrane potential,, and GnRH release in GT1-7 cells. We will determine
the concentration dependence of acute ethanol treatment on these GABA(A)
mediated functions.
StatusFinished
Effective start/end date8/1/947/31/98

Funding

  • National Institutes of Health: $138,011.00
  • National Institutes of Health
  • National Institutes of Health: $127,600.00

ASJC

  • Medicine(all)

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