GABAA receptors mediate fast inhibitory neurotransmission in the brain. Dysfunction of these receptors is associated with various psychiatric/neurological disorders and drugs targeting this receptor are widely used therapeutic agents. Both the efficacy and plasticity of GABAA receptor-mediated neurotransmission depends on the number of surface GABAA receptors. An understudied aspect of receptor...

Temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) is a form of focal epilepsy, which is particularly resistant to medical treatment. It is, however, established that patients with TLE and HS respond favorably to surgery. Accumulating evidence indicates that TLE is associated with impairment in synaptic signaling via GABA (γ-aminobutyric acid), the main inhibitory neurotran...

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-...

Transient lower esophageal sphincter (LES) relaxation is the major mechanism of gastroesophageal reflux. This study uses an established ferret model to evaluate GABAB receptor agonists' ability to reduce triggering of transient LES relaxations. One hundred sixty manometric/pH studies were performed on 18 conscious ferrets. In untreated animals, intragastric infusion of 25 ml glucose (pH 3.5) le...

Modulation of receptor trafficking is critical for controlling neurotransmission. A γ2(R43Q) point mutation on GABAA receptor subunit is linked to epilepsy in human. We recently analyzed the effect of this amino-acid substitution on GABAA receptor trafficking and showed that this mutation as well as agonist application, both affecting GABAA receptor extracellular domain, have an effect on recep...

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...

Several groups have characterized the pharmacology of 4or 6 3 -containing GABAA receptors expressed in different cell systems. We have previously demonstrated that the pharmacological profiles of a series of GABAA receptor agonists are highly dependent on the subunit and little on the and subunits, so to further understand the contribution of the different subunits in the GABAA receptor complex...

Wu J, Chang Y, Li G, Xue F, DeChon J, Ellsworth K, Liu Q, Yang K, Bahadroani N, Zheng C, Zhang J, Rekate H, Rho JM, Kerrigan JF. Electrophysiological properties and subunit composition of GABAA receptors in patients with gelastic seizures and hypothalamic hamartoma. J Neurophysiol 98: 5–15, 2007. First published April 11, 2007; doi:10.1152/jn.00165.2007. Abnormalities in GABAA receptor structur...

Presynaptic inhibition onto axons regulates neuronal output, but how such inhibitory synapses develop and are maintained in vivo remains unclear. Axon terminals of glutamatergic retinal rod bipolar cells (RBCs) receive GABAA and GABAC receptor-mediated synaptic inhibition. We found that perturbing GABAergic or glutamatergic neurotransmission does not prevent GABAergic synaptogenesis onto RBC ax...

On most adrenergic and cholinergic nerve terminals, prejunctional α-adrenoceptors belonging to the α2-subtype have been identified. Activation of these receptors will decrease the release of norepinephrine. It has been reported that several isolated tissue preparations contain prejunctional dopamine receptors, the stimulation of which inhibits neurotransmission. It has remained uncertain whethe...