Presynaptic GABAA receptors modulate synaptic transmission in several areas of the CNS but are not known to have this action in the cerebral cortex. We report that GABAA receptor activation reduces hippocampal mossy fibers excitability but has the opposite effect when intracellular Cl- is experimentally elevated. Synaptically released GABA mimics the effect of exogenous agonists. GABAA receptor...

Zarnowska ED, Keist R, Rudolph U, Pearce RA. GABAA receptor 5 subunits contribute to GABAA,slow synaptic inhibition in mouse hippocampus. J Neurophysiol 101: 1179–1191, 2009. First published December 10, 2008; doi:10.1152/jn.91203.2008. -Aminobutyric acid type A (GABAA) receptor 5 subunits, which are heavily expressed in the hippocampus, are potential drug targets for improving cognitive functi...

GABAA receptors are ligand-gated ion channels that mediate inhibitory synaptic signaling in the CNS. Fluorescent probes with the ability to target these receptors can provide insights into receptor location, distribution and dynamics in live cells, while revealing abnormalities in their distribution and dynamics that could occur in a variety of diseases. We have developed fluorescent probes of ...

Anesthetics appear to produce neurodepression by altering synaptic transmission and/or intrinsic neuronal excitability. Propofol, a widely used anesthetic, has proposed effects on many targets, ranging from sodium channels to GABAA inhibition. We examined effects of propofol on the intrinsic excitability of hippocampal CA1 neurons (primarily interneurons) recorded from adult rat brain slices. P...

The neurotransmitter gamma-aminobutyric acid (GABA) inhibits the activity of signal-receiving neurons by interacting with the GABAA receptor on these cells. The GABAA receptor is a channel-forming protein that allows the passage of chloride ions into the cells. Excessive GABAA activation may play a role in mediating the sedative effects of alcohol and other sedating and anesthetic agents. For e...

Recent advances in molecular biology and complementary information derived from neuropharmacology, biochemistry and behavior have dramatically increased our understanding of various aspects of GABAA receptors. These studies have revealed that the GABAA receptor is derived from various subunits such as alpha1-alpha6, beta1-beta3, gamma1-gamma3, delta, epsilon, pi, and rho1-3. Furthermore, two ad...

GABAA receptors mediate fast phasic inhibitory postsynaptic potentials and participate in slower tonic extrasynaptic inhibition. Thy1alpha6 mice with ectopic forebrain expression of GABAA receptor alpha6 subunits exhibit increased extrasynaptic GABAA receptor-mediated background conductance and reduced synaptic GABAA receptor currents in hippocampal CA1 neurons [W. Wisden et al. (2002) Neuropha...

The clinical need for novel bronchodilators for the treatment of bronchoconstrictive diseases remains a major medical issue. Modulation of airway smooth muscle (ASM) chloride via GABAA receptor activation to achieve relaxation of precontracted ASM represents a potentially beneficial therapeutic option. Since human ASM GABAA receptors express only the α4- and α5-subunits, there is an opportunity...