GABA A receptors are Cl Ϫ channels that can be opened by GABA and are the major inhibitory neurotransmitter receptors in the CNS. A variety of pharmacologically important drugs, such as benzodiazepines, barbiturates, neuroactive steroids, anesthetics and convulsants, produce at least part of their clinically relevant effects by interacting with distinct allosteric binding sites on GABA A recept...

The barbiturate phenobarbital has been in use in the treatment of epilepsy for 100 years. It has long been recognized that barbiturates act by prolonging and potentiating the action of γ-aminobutyric acid (GABA) on GABA(A) receptors and at higher concentrations directly activating the receptors. A large body of data supports the concept that GABA(A) receptors are the primary central nervous sys...

GABAergic IPSCs have a relatively slow decay (deactivation) that appears to result from GABA(A) receptor channel openings that occur well beyond the predicted duration of free GABA at central synapses. Open and desensitized states have been suggested to prevent dissociation of agonist from the receptor, thus prolonging deactivation. However, simultaneous assessment of GABA binding and channel g...

gamma-Aminobutyric acid type B (GABA(B)) receptors mediate the metabotropic actions of the inhibitory neurotransmitter GABA. These seven-transmembrane receptors are known to signal primarily through activation of G proteins to modulate the action of ion channels or second messengers. The functional GABA(B) receptor is made up of a heterodimer consisting of two subunits, GABA(B)-R1 and GABA(B)-R...

Most sedative-hypnotics used in insomnia treatment target the gamma-aminobutyric acid (GABA)(A) receptors. A vast repertoire of GABA(A) receptor subtypes has been identified and displays specific electrophysiological and functional properties. GABA(A)-mediated inhibition traditionally refers to 'phasic' inhibition, arising from synaptic GABA(A) receptors which transiently inhibit neurons. Howev...

Speed and reliability of synaptic transmission are essential for information coding in neuronal networks and require the presence of clustered neurotransmitter receptors at the plasma membrane in precise apposition to presynaptic terminals. Receptor clusterization is the result of highly regulated processes involving functional and structural proteins. Among the structural elements, microtubule...

We studied the cellular and subcellular distribution of GABA(A) receptors in the Bergmann glia and Purkinje cells in the molecular layer of the cerebellum by using electron microscopy postembedding immunogold techniques. Gold particles corresponding to alpha2 and gamma1 immunoreactivity were localized in Bergmann glia processes that wrapped Purkinje cell somata, dendritic shafts, and some dendr...

Neal and Cunningham (Neal, M. J., and J. R. Cunningham. 1995. J. Physiol. (Lond.). 482:363-372) showed that GABA(B) agonists and glycinergic antagonists enhance the light-evoked release of retinal acetylcholine. They proposed that glycinergic cells inhibit the cholinergic Starburst amacrine cells and are in turn inhibited by GABA through GABA(B) receptors. However, as recently shown, glycinergi...

In the vertebrate brain, inhibition is largely mediated by γ-aminobutyric acid (GABA). This neurotransmitter comprises a signaling machinery of GABAA, GABAB receptors, transporters, glutamate decarboxylases (gads) and 4-aminobutyrate aminotransferase (abat), and associated proteins. Chloride is intimately related to GABAA receptor conductance, GABA uptake, and GADs activity. The response of tar...

GABA type A (GABA(A)) receptors are functionally regulated by external protons in a manner dependent on the receptor subunit composition. Although H(+) can regulate the open probability of single GABA ion channels, exactly what residues and receptor subunits are responsible for proton-induced modulation remain unknown. This study resolves this issue by using recombinant alpha1betai subunit GABA...