Dohi, Akiko, ERK/MAPK Pathway Regulation of GABAA Receptor Function. Doctor of Philosophy (Pharmacology and Neuroscience), December, 2009, pp116, 23 illustrations, 6 supplemental illustrations, bibliography, 158 titles. GABAA receptor is a ligand-gated ion channel that conducts negatively charged chloride ions. Influx of this ion leads to hyperpolarization of neurons; thus, suppression of the n...

Activation of chloride gated GABAA receptors regulates the excitatory transmission in the epileptic brain. Positive allosteric modulation of these receptors via distinct recognition sites is the therapeutic mechanism of antiepileptic agents which prevents the hyperexcitability associated with epilepsy. These distinct sites are based on subunit composition which determines binding of various dru...

Inhibition of GABAA receptors by Cu(2+) has been appreciated for some time, but differences between synaptic and extrasynaptic GABAA receptors have not been explored. We show that Cu(2+) potently blocks steady-state GABA currents mediated by extrasynaptic δ subunit-containing GABAA receptors (δ-GABAARs) with an IC50 of 65 nM. This compares with an IC50 of 85 μM for synaptic γ subunit-containing...

Any given subunit of the heteromultimeric type-A gamma-aminobutyric acid (GABA) GABAA receptor may be present in several receptor subtypes expressed by individual neurons. Changes in the expression of a subunit may result in differential changes in the expression of other subunits depending on the subunit composition of the receptor subtype, leading to alterations in neuronal responsiveness to ...

BackgroundMultiple cognitive and psychiatric disorders are associated with an increased tonic inhibitory conductance that is generated by ?5 subunit-containing ?-aminobutyric acid type A (?5 GABAA) receptors. Negative allosteric modulators inhibit GABAA receptors (?5-NAMs) being developed as treatments for these disorders. The effects of ?5-NAMs have been studied on recombinant expressed in non...

SCOPE GABAA receptors are modulated by Sideritis extracts. The aim of this study was to identify single substances from Sideritis extracts responsible for GABAA receptor modulation. METHODS AND RESULTS Single volatile substances identified by GC have been tested in two expression systems, Xenopus oocytes and human embryonic kidney cells. Some of these substances, especially carvacrol, were hi...

Gamma-aminobutyric acid type A (GABAA) receptors expressed within the medial preoptic area (mPOA) are known to play a critical role in regulating sexual and neuroendocrine functions. In the rat brain, high levels of expression of the gamma1 subunit mRNA of the GABAA receptor are restricted to a limited number of regions that mediate sexual behaviors, including the mPOA. The biophysical and phar...

The parahippocampal areas including the subiculum, pre- and parasubiculum, and notably the entorhinal cortex (EC) are intimately involved in the generation of limbic seizures in temporal lobe epilepsy. We investigated changes in the expression of 10 major GABAA receptor subunit mRNAs in subfields of the ventral hippocampus, ventral subiculum, EC, and perirhinal cortex (PRC) at different interva...

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...

GABAA receptors are predominantly composed of and isoforms in the brain. It has been proposed that receptors mediate phasic inhibition, whereas receptors mediate tonic inhibition. Propofol (2,6-di-isopropylphenol), a widely used anesthetic drug, exerts its effect primarily by modulating GABAA receptors; however, the effects of propofol on the kinetic properties of and receptors are uncertain. W...