Astroglial Cells Express Large Amounts of GABA_A Receptor Proteins in Mature Brain

Abstract

GABAA receptors were characterized in cellular fractions isolated from adult bovine brain. The fraction enriched in cortical astrocytes is very rich in high‐affinity binding sites for [3H]flunitrazepam and other “central‐type” benzodiazepine ligands. The amount of specific [3H]flunitrazepam binding was more than five times higher in the glial fraction than in synaptosomal and perikaryal fractions. [3H]Flunitrazepam was displaced by low concentrations of clonazepam and other specific ligands for central GABAA receptors. Specific binding sites for GABA, flunitrazepam, barbiturates, and picrotoxin‐like convulsants were characterized. Allosteric interactions between the different sites were typical of central‐type GABAA receptors. The presence of α‐subunit(s), as revealed by [3H]flunitrazepam photoaffinity labeling, was demonstrated in all brain fractions at molecular mass 51–53 kDa. Photoaffinity labeling was highest in the glial fraction. However, in primary cultured astrocytes from neonate rat cortex, no photoaffinity labeling was detected. Information obtained from astrocytes in culture should thus be taken with caution when extrapolated to differentiated astroglial cells. Our results actually show that, in mature brain, most of the fully pharmacologically active GABAA receptors are extrasynaptic and expressed in astroglia.

Chronic Prenatal Ethanol Exposure Increases GABAAReceptor Subunit Protein Expression in the Adult Guinea Pig Cerebral Cortex

“…Affected cell types in the cerebral cortex may include GABAergic interneurons, glutamatergic pyramidal cells, or glial cells (Bureau et al, 1995;Hornung and Fritschy, 1996). Chronic prenatal exposure to ethanol in the rat decreases neuronal and glial cell number in the somatosensory cortex of adult offspring (Miller and Potempa, 1990) and, more specifically, in the number of parvalbuminpositive neurons in the cingulate cortex, an index of normally functioning GABAergic neurons (Moore et al, 1998).…”

Arundic Acid (ONO-2506) Ameliorates Delayed Ischemic Brain Damage by Preventing Astrocytic Overproduction of S100B

“…GABA A receptors are expressed at high levels in astrocytes of the mature brain [118]. Although there are some reports showing that GABA A receptors are scarcely expressed in cultured astrocytes [119][120][121][122], expression of GABA A /benzodiazepine receptors has been shown electrophysiologically, immunohistochemically, and biochemically in studies using cultured astrocytes [123], brain slices [124], acutely isolated hippocampal slices [125], and membrane fractions of the mature brain [118].…”

“…Although there are some reports showing that GABA A receptors are scarcely expressed in cultured astrocytes [119][120][121][122], expression of GABA A /benzodiazepine receptors has been shown electrophysiologically, immunohistochemically, and biochemically in studies using cultured astrocytes [123], brain slices [124], acutely isolated hippocampal slices [125], and membrane fractions of the mature brain [118]. It is important to note that reactive astrocytes have little or no immunoreactivity for GABA A receptors [126], consonant with our observations in the rat model of cerebral ischemia [112,127].…”

Bicarbonate efflux via GABAA receptors depolarizes membrane potential and inhibits two‐pore domain potassium channels of astrocytes in rat hippocampal slices

“…The functional GABA A -Rs are pentamer assembling from 19 subunits (α1-6, β1-3, γ1-3, δ, ε, θ, π and ρ1-3) into different subtypes (Olsen and Sieghart 2008). The expression of ionotropic GABA A -R in astrocytes has been indicated by immunocytochemistry (Bureau et al 1995) and functional studies, including GABA A -R currents measured from astrocytes in situ (Bekar et al 1999; MacVicar et al 1989; Meier et al 2008; Steinhauser et al 1994) and in acutely isolated preparation of rat hippocampus (Fraser et al 1995; Zhou and Kimelberg 2001). Activation of astrocytic GABA A -R has been shown to elevate intracellular Ca 2+ concentration (Bernstein et al 1996; Fraser et al 1995; Meier et al 2008) and modulate outward K + channel activity (Bekar and Walz 1999; Bekar and Walz 2002).…”