We examined the effects of the neurosteroid pregnenolone sulfate (PS) on GABA(A) receptor-mediated synaptic currents and currents elicited by rapid applications of GABA onto nucleated outside-out patches in cultured postnatal rat hippocampal neurons. At 10 microm, PS significantly depressed peak responses and accelerated the decay of evoked inhibitory synaptic currents. In nucleated outside-out...

Following the recent discovery that GABA receptors expressed in cell lines are only functional when both GABA and GABA are B B1 B2 expressed, the present study reports on the development of polyclonal antisera specific for carboxyl-terminal portions of the two related GABA receptor components respectively. Western blotting indicated the specificity of affinity-purified antibodies for native or ...

The Cys-loop family of ligand-gated ion channels contains both vertebrate and invertebrate members that are activated by GABA (gamma-aminobutyric acid). Many of the residues that are critical for ligand binding have been identified in vertebrate GABA(A) and GABA(C) receptors, and specific interactions between GABA and some of these residues have been determined. In the present paper, I show how...

The amygdala is intimately involved in emotional behavior, and its role in the generation of anxiety and conditioned fear is well known. Benzodiazepines, which are commonly used for the relief of anxiety, are thought to act by enhancing the action of the inhibitory transmitter GABA. We have examined the properties of GABA-mediated inhibition in the amygdala. Whole-cell recordings were made from...

GABA(B) receptor function is upregulated in the paraventricular nucleus (PVN) of the hypothalamus in spontaneously hypertensive rats (SHR), but it is unclear whether this upregulation occurs pre- or postsynaptically. We therefore determined pre- and postsynaptic GABA(B) receptor function in retrogradely labeled spinally projecting PVN neurons using whole cell patch-clamp recording in brain slic...

The gamma-aminobutyric acid-A (GABA(A)) receptor complex is allosterically modulated by a variety of substances, some of clinical importance. Barbiturates and neurosteroids augment GABA-currents and also directly gate the channel. A variety of gamma-butyrolactone analogues also modulate GABA-induced currents, with some potentiating and others inhibiting. Because several gamma-thiobutyrolactone ...

gamma-aminobutyric acid (GABA) plays important roles in the central nervous system, acting as a neurotransmitter on both ionotropic ligand-gated Cl(-)-channels, and metabotropic G-protein coupled receptors (GPCRs). These two types of receptors called GABA(A) (and C) and GABA(B) are the targets of major therapeutic drugs such as the anxiolytic benzodiazepines, and antispastic drug baclofen (lior...

Treatment with pentobarbital of primary cultured cerebellar granule cells decreased the gamma-aminobutyric acid, (GABA)A receptor subunit gamma-2 long/short (gamma-2L/S) mRNA ratio. A high dose of pentobarbital (500 microM) decreased the gamma-2L/S ratio by 64%; the decrease was dose and time dependent and reversible. (-)-Hexobarbital (500 microM), the less potent stereoisomer for GABA(A) recep...

Neurosteroids represent a class of endogenous steroids that are synthesized in the brain, the adrenals, and the gonads and have potent and selective effects on the GABAA-receptor. 3α-hydroxy A-ring reduced metabolites of progesterone, deoxycorticosterone, and testosterone are positive modulators of GABA(A)-receptor in a non-genomic manner. Allopregnanolone (3α-OH-5α-pregnan-20-one), 5α-androsta...

Although 3alpha-substituted metabolites of progesterone are well established to interact with GABA(A) receptor/Cl(-) channels, the nature of the interaction(s) remains uncertain. We used patch-clamp recording to study the interaction with GABA(A) receptor/Cl(-) channels expressed by embryonic hippocampal neurons differentiating in culture and nonneuronal cells transfected with GABA(A) receptor ...