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Rapid Down‐Regulation of GABA A Receptors in the Gerbil Hippocampus Following Transient Cerebral Ischemia
Author(s) -
Alicke Bruno,
SchwartzBloom Rochelle D.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65062808.x
Subject(s) - gerbil , receptor , dentate gyrus , hippocampal formation , hippocampus , gabaa receptor , agonist , ischemia , medicine , endocrinology , flumazenil , flunitrazepam , chemistry , biology , pharmacology
During transient cerebral ischemia, there is a temporary and robust accumulation of extracellular GABA in the hippocampus. We examined whether the acute exposure of GABA A /benzodiazepine receptors to high concentrations of GABA early after ischemia results in receptor down‐regulation as observed in vitro. Gerbils were killed 30 and 60 min following a 5‐min bilateral carotid occlusion, and their brains were prepared for receptor autoradiography. The hydrophilic GABA A receptor antagonist [ 3 H]SR‐95531 and the hydrophobic benzodiazepine agonist [ 3 H]flunitrazepam were used to distinguish between cell surface and internalized receptors. Ischemia significantly decreased [ 3 H]SR‐95531 binding in hippocampal areas CA1 and CA3 and in the dentate gyrus 30 min after ischemia. Scatchard analysis in area CA1 revealed that ischemia decreased the B max as low as 44%. The affinity of the remaining sites was increased substantially (72% decrease in K D ). As expected, there were no changes in the binding of [ 3 H]flunitrazepam to hippocampus in the early postischemic period because the benzodiazepine could bind to both internalized receptors and those on the cell surface. We hypothesize that prolonged exposure (∼30–45 min) of GABA A receptors to high concentrations of synaptic GABA in vivo causes receptor down‐regulation, perhaps via receptor internalization.