gamma-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in brain, is known to interact with a subclass of receptors that activate a ligand-gated chloride ion channel. Exposure of cultured embryonic chick neurons to physiological concentrations of GABA results in a time-dependent down-regulation of these GABAA receptors. To delineate the cellular mechanism(s) responsible for agonis...

The inhibitory neurotransmitter !-aminobutyric acid (GABA) has multiple receptors. In mammals, the GABAA receptor subtype is modulated by neurosteroids. However, whether steroid interaction with the GABAA receptor is unique to mammals or a conserved feature in vertebrates is unknown. Thus, neurosteroid modulation of the GABAA receptor was investigated in the brain of the bullfrog (Rana catesbei...

Benzodiazepines (BDZ) are widely used in clinics the treatment of psychiatric disorders, and their main action is considered to be determined by more selective binding with ?1, ?2, ?3 or ?5 subunits GABA receptor.
 The aim this work was studying molecular mechanism new analgesic – propoxazepam its metabolite (3-hydroxypropoxazepam) on ?3, ?4 containing GABAA channels.
 Materials metho...

The levels of several GABAA receptor subunit mRNAs increase as cerebellar granule neurons migrate to their adult positions and receive excitatory mossy fiber input. Despite the temporal similarity of these increases in transcript expression in vivo, studies in cultured granule neurons demonstrated that the subunit mRNAs are differentially regulated. To address the possibility that neuronal acti...

Domestic Mongolian gerbils, a model of inherited epilepsy, begin having spontaneous seizures at ~1.5 months of age, making it possible to evaluate them during epileptic and pre-epileptic stages. Previous studies have shown that GABA-binding is reduced in the substantia nigra pars reticulata (SNr) of both epileptic and pre-epileptic gerbils compared with controls, suggesting that reduced express...

Ionotropic receptors are tightly regulated by second messenger systems and are often present along with their metabotropic counterparts on a neuron's plasma membrane. This leads to the hypothesis that the two receptor subtypes can interact, and indeed this has been observed in excitatory glutamate and inhibitory GABA receptors. In both systems the metabotropic pathway augments the ionotropic re...

Attenuated behavioral sensitivity to neurosteroids has been reported for mice deficient in the GABAA receptor subunit. We therefore investigated potential subunit-specific neurosteroid pharmacology of the following GABAA receptor isoforms in a transient expression system: 1 3 2L, 1 3 , 6 3 2L, and 6 3 . Potentiation of submaximal GABAA receptor currents by the neurosteroid tetrahydrodeoxycortic...

The effects of a single convulsive dose of pentylenetetrazol (PTZ, 45 mg/kg i.p.) on rat brain gamma-aminobutyric acid type A (GABAA) receptors were studied. Selected GABAA receptor subunit mRNAs were measured by Northern blot analysis (with beta-actin mRNA as a standard). Four hours after PTZ, the GABAA receptor gamma2-mRNA was decreased in hippocampus, cerebral cortex, and cerebellum; alpha1-...

Propofol, an intravenous anesthetic, is a positive modulator of the GABAA receptor, but the mechanistic details, including the relevant binding sites and alternative targets, remain disputed. Here we undertook an in-depth study of alkylphenol-based anesthetic binding to synaptic membranes. We designed, synthesized, and characterized a chemically active alkylphenol anesthetic (2-((prop-2-yn-1-yl...

The tubulin-binding protein gephyrin copurifies with the inhibitory glycine receptor (GlyR) and is essential for its postsynaptic localization. Here we have analyzed the interaction between the GlyR and recombinant gephyrin and identified a gephyrin binding site in the cytoplasmic loop between the third and fourth transmembrane segments of the I] subunit. GlyR a subunits and GABAA receptor prot...