| PMID |
Passage |
MeSH |
| 9453541 |
GABA induced an increase in intracellular calcium
concentration, indicating the presence of functional receptors for this
transmitter. Characterization of the GABA-evoked calcium response and
whole-cell currents indicated that these responses were mediated by
GABA(A) receptors. Reverse transcription-polymerase chain reaction
revealed differential expression of mRNAs for specific GABA(A) receptor
subunits. Messages for the alpha2, alpha4, beta1, and delta subunits
were readily detected by reverse transcription-polymerase chain
reaction, |
Calcium Signaling; Gene Expression; Neural Conduction |
| 9622011 |
It is possible that the three GABA(A) receptor subunits
(alpha4, beta1, and gamma1) found in precursor cells form the Cl-
channels detected electrophysiologically. The functional GABA(A)
receptor/Cl- channels and associated regulation of their cytoplasmic
Ca2+ levels via bicuculline-sensitive mechanisms may play significant
roles in the regulation of neural cell proliferation in this model
neuroepithelium. |
Calcium Signaling; Chloride Channels; Ion Channel
Gating |
| 10366626 |
Biophysical analyses of GABA-activated Cl currents in ZI
cells
revealed two types of receptor-coupled channel properties: one
comprising short-lasting openings, high affinity for GABA, and low
sensitivity to diazepam, and the other with long-lasting openings, low
affinity for GABA, and high sensitivity to diazepam. Both types of
channel activity were found in the same cell. Channel kinetics were
well modeled by fitting dwell time distributions to biliganded
activation and included two open and five closed states. We propose
that short- and long-lasting openings correspond to GABAA receptor/Cl
channels containing 412 and 512 subunits, respectively. |
Chloride
Channels; Ion Channel Gating |
| 10493732 |
Clonazepam augmentation correlated positively with the
relative expression of 1- and 2-mRNAs and negatively with 4- and
-mRNAs. These data demonstrate that specific GABAR subunit mRNAs
exhibit coordinated control of expression in individual DGCs, which has
significant impact on inhibitory function. |
Gene Expression; Dentate
Gyrus |
| 11050117 |
Constitutive Endocytosis of GABAA Receptors by an Association
with the Adaptin AP2 Complex Modulates Inhibitory Synaptic Currents in
Hippocampal Neurons |
Hippocampus; Endocytosis |
| 11264309 |
During migration from the VZ/SVZ to the CP/SP,
differentiating
cortical neurons became predominantly GABAergic, and their dominant
GABAA receptor subunit expression pattern changed from 411 to 3323
coincident with an increasing potency of GABA on GABAA
receptor-mediated depolarization. |
Cell Movement |
| 11489254 |
alpha4 upregulation was inversely correlated with BDZ
potentiation of GABA-gated current, assessed using whole cell patch
clamp techniques on acutely isolated hippocampal pyramidal cells. A
near total BDZ insensitivity was observed by 2-3 days of hormone
exposure in association with the maximal increase in alpha4
levels |
Hippocampus/drug effects; Gene Expression |
| 12522171 |
following neuroactive steroid exposure, a subpopulation of
synaptic GABARs pharmacologically characterized as 4-containing decay
more quickly than BDZ-responsive synaptic currents. Conversely, states
that decrease expression of the 4 subunit are characterized by
increases in GABAR-mediated Cl flux (Papadeas et al. 2001). |
Ion
Channel Gating |
| 14684873 |
flumazenil, a partial inverse agonist and antagonist,
respectively, in control cells, both acted as positive modulators of
GABA responses after discontinuation of prolonged ethanol treatment,
consistent with the notion that ethanol withdrawal increases the
abundance of GABAA receptors containing the 4 subunit. |
Ion Channel
Gating |
| 14966300 |
In conclusion, the results presented in this manuscript
demonstrate that 4ß22 and 4ß2 receptors are activated by
GABA and PB.
The strong responses seen in the presence of PB suggest a role for 4
subunit-containing receptors in PB-mediated effects in the mammalian
nervous system. The presumed extrasynaptic location of the 4ß2
receptors makes these receptors an attractive target of barbiturates in
controlling tonic inhibitory conductance. |
Phenobarbital; Neural
Conduction |
| 15199051 |
Here we describe the identification and functional
characterization of four-amino acid motifs specific for individual
subunits of the GABAA receptor, which control the sensitivity to GABA
of the resulting receptor. Exchange between subunits of the whole motif
but not of single amino acids resulted in transfer of the respective
GABA sensitivities for most receptors of the general composition i32,
where i ranges from 1 to 6. Thus, our findings may provide insight into
the mechanistic features responsible for the molecular diversity of
GABAergic neurotransmission and deliver tools to further dissect the
biological significance of GABAA receptor heterogeneity. |
Neural
Conduction |
| 8578436 |
Increasing evidence points to an important role for GABA in
epilepsy and various neuropsychiatric disorders. Recent advances in
molecular biology and complementary information derived from
pharmacology, biochemistry, electrophysiology, anatomy and cell
biology, and behavior have led to a phenomenal growth in our
understanding of the structure, function, regulation, and evolution of
the GABAA receptor. Benzodiazepines, barbiturates, steroids, polyvalent
cations, and ethanol act as positive or negative modulators of receptor
function. The description of a receptor gene superfamily comprising the
subunits of the GABAA, nicotinic acetylcholine, and glycine receptors
has led to a new way of thinking about gene expression and receptor
assembly in the nervous system. Seventeen genetically distinct subunit
subtypes (alpha 1-alpha 6, beta 1-beta 4, gamma 1-gamma 4, delta,
p1-p2) and alternatively spliced variants contribute to the molecular
architecture of the GABAA receptor. |
Neuropsychology |
| 9582073 |
Here we report a progesterone-withdrawal paradigm, designed
to
mimic PMS and post-partum syndrome in a rat model. In this model,
withdrawal of progesterone leads to increased seizure susceptibility
and insensitivity to benzodiazepine sedatives through an effect on gene
transcription. Specifically, this effect was due to reduced levels of
3alpha,5alpha-THP which enhance transcription of the gene encoding the
alpha4 subunit of the GABA(A) receptor. We also find that increased
susceptibility to seizure after progesferone withdrawal is due to a
sixfold decrease in the decay time for GABA currents and consequent
decreased inhibitory function. Blockade of the alpha4 gene transcript
prevents these withdrawal properties. PMS symptoms may therefore be
attributable, in part, to alterations in expression of GABA(A) receptor
subunits as a result of progesterone withdrawal. |
Premenstrual Syndrome;
Seizures; Gene Expression; Progesterone; Neural Conduction |
| 9651210 |
This withdrawal profile is similar to that reported for other
GABAA-modulatory drugs such as the benzodiazepines (BDZs),
barbiturates, and ethanol. These changes were also associated with
significant two and threefold increases in both the mRNA and protein
for the 4 subunit of the GABAA receptor, respectively, in hippocampus.
The pseudopregnancy paradigm may be a useful model for periods of
endogenous 3,5-THP withdrawal such as premenstrual syndrome and
postpartum or postmenopausal dysphoria, when increased emotional
lability and BDZ insensitivity have been reported. |
Gene Expression;
Hippocampus; Premenstrual Syndrome; Pseudopregnancy |
| 9685573 |
Further, no significant differences were found between groups
in the mRNA levels for the alpha3 subunit, alpha4 subunit, GAD65, and
GAD67. These results suggest that the behaviors related to conflict and
uncontrollable aversive stimuli (yoked control group) are accompanied
and perhaps mediated by selective changes in the GABAA alpha1 or alpha2
subunits, respectively. |
Punishment; Conflict (Psychology); Gene
Expression |
| 10461213 |
Disorders of inappropriate or excessive anxiety can be
treated
with benzodiazepine agonists, such as Valium, which bind to the subunit
of the GABAA receptor and increase inhibition. There is
considerable evidence for abnormal GABA receptor function in panic
disorder9. |
Anxiety |
| 11489254 |
Up-regulation of the alpha4 GABAR subunit was also reflected
by an increase in anxiety in the elevated plus maze. |
Anxiety; Gene
Expression |
| 11495904 |
For GABAA receptors containing 4 subunits, our experiments
reveal that inclusion of instead of 2 subunits can increase the
affinity and in some cases the efficacy of agonists and can increase
the efficacy of allosteric modulators. Pregnanolone was a particularly
efficacious modulator of 43 receptors, consistent with a central role
for this subunit combination in premenstrual syndrome. |
Premenstrual
Syndrome; Gene Expression; Allosteric Regulation |
| 12581182 |
The sex differences in the ASR were paralleled by sex
differences in the expression of the GABAA-R alpha4 subunit in the
amygdala such that alpha4 subunit expression was up-regulated in
females during PWD whereas alpha4 levels in males undergoing PWD were
not altered relative to controls. These findings might have
implications regarding gender differences in human mood disorders and
the aetiology of premenstrual anxiety. |
Anxiety; Progesterone; Amygdala |
| 12606703 |
However, continuous exposure to progesterone increases
anxiety
in association with increased expression of the |
Anxiety; Progesterone |
| 12702713 |
Previous studies in mice with a targeted disruption of the
subunit revealed a considerable attenuation of behavioral responses to
neuroactive steroids but not to other neuromodulatory drugs. Here we
show that subunit loss leads to a concomitant reduction in
hippocampal 4 subunit levels. |
Hippocampus |
| 14960621 |
In addition, mRNA of the 1, 3, 4, and receptor subunits was
reduced in the frontopolar region of suicide victims. Interestingly, a
partial analysis of the GABAA receptor functional genome revealed high
cross-correlations between subunit expression in cortical regions of
nondepressed individuals, suggesting a high degree of coordinated gene
regulation. However, in suicide brains, this regulation was perturbed,
independent of overall subunit abundance. These findings raise the
possibility that the CRH and GABAA receptor subunit changes, or the
disturbed coordination between these GABAA receptor subunits,
contribute to depression and/or suicidality or are secondary to the
illness/distress associated with it. |
Suicide; Gene Expression |
| 15280440 |
There were no changes in 4 mRNA levels. |
Gene Expression |
| 15708482 |
Increased expression of alpha4beta1delta GABA(A) receptors in
the interneurones of the PAG could render the panic circuitry
abnormally excitable by disinhibiting the ongoing GABAergic inhibition.
Similar changes in neuronal excitability within the PAG in women
consequent to falling steroid levels in the late luteal phase of the
menstrual cycle could contribute to the development of pre-menstrual
dysphoria. |
Periaqueductal Gray; Gene Expression; Premenstrual Syndrome;
Panic |