The GABAA receptors are the major inhibitory receptors in the brain and are localized at both synaptic and extrasynaptic membranes. Synaptic GABAA receptors mediate phasic inhibition, whereas extrasynaptic GABAA receptors mediate tonic inhibition. Both phasic and tonic inhibitions regulate neuronal activity, but whether they regulate each other is not very clear. Here, we investigated the funct...

Huang, Ren-Qi, Zhenglan Chen, and Glenn H. Dillon. Molecular basis for modulation of recombinant 1 2 2 GABAA receptors by protons. J Neurophysiol 92: 883–894, 2004. First published March 17, 2004; 10.1152/jn.01040.2003. We have previously shown that extracellular protons inhibit recombinant and native GABAA receptors. In this report, we studied the site(s) and mechanism by which protons modulat...

Gamma-aminobutyric acid (GABA) depolarizes dorsal root ganglia (DRG) primary afferent neurons through activation of Cl- permeable GABAA receptors but the physiologic role of GABAA receptors in the peripheral terminals of DRG neurons remains unclear. In this study, we investigated the role of peripheral GABAA receptors in nociception using a mouse model of acute inflammation. In vivo, peripheral...

GABA is the principal inhibitory neurotransmitter in the mammalian CNS. It acts via two classes of receptors, the GABAA, a ligand gated ion channel (ionotropic receptor) and the metabotropic G-protein coupled GABAB receptor. While synaptic GABAA receptors underlie classical ‘phasic’ GABAA receptor-mediated inhibition, extrasynaptic GABAA receptors (eGABAAR) mediate a new form of inhibition, ter...

Ethanol is a chemically simple compound that produces many well-known effects in humans. The prevailing idea for many years was that ethanol and other alcohols exerted their effects on the central nervous system (CNS) by non-selectively disrupting the lipid bilayers of neurons. However, in recent years, there has been an accumulation of evidence pointing to the importance of ligand-gated ion ch...

Diazepam is used clinically for its myorelaxant, anxiolytic, sedative, and anticonvulsant properties. Although the anxiolytic action is mediated by a2 g-aminobutyric acid A (GABAA) receptors, the sedative action and in part the anticonvulsant action are mediated by a1 GABAA receptors. To identify the GABAA receptor subtypes mediating the action of diazepam on muscle tone, we have assessed the m...

Many inhaled anesthetics enhance the effect of the inhibitory neurotransmitter gamma aminobutyric acid (GABA), supporting the view that the GABAA receptor could mediate the capacity of inhaled anesthetics to produce immobility in the face of noxious stimulation (i.e., MAC, the minimum alveolar concentration required to suppress movement in response to a noxious stimulus in 50% of subjects). How...

UNLABELLED The ventrolateral periaqueductal gray (vlPAG) is a key structure in the descending pain modulatory circuit. Activation of the circuit occurs via disinhibition of GABAergic inputs onto vlPAG output neurons. In these studies, we tested the hypothesis that GABAergic inhibition is increased during persistent inflammation, dampening activation of the descending circuit from the vlPAG. Our...

Benzodiazepine (BZ) binding site ligands are important central nervous system (CNS) drugs. Their numbers and our knowledge of how they interact with the BZ-binding site of GABAA receptors are both rapidly expanding. The GABAA receptor is a member of the ligand-gated ion channel superfamily. In general, it consists of an assembly of transmembrane pentamers of different subunit compositions (1). ...

The efficacy of fast synaptic inhibition is critically dependent on the accumulation of GABAA receptors at inhibitory synapses, a process that remains poorly understood. Here, we examined the dynamics of cell surface GABAA receptors using receptor subunits modified with N-terminal extracellular ecliptic pHluorin reporters. In hippocampal neurons, GABAA receptors incorporating pHluorin-tagged su...