Increasing hepatocyte membrane potentials by augmenting GABAergic activity inhibits nonmalignant hepatocyte proliferative activity. The objectives of this study were to document 1) potential differences (PDs) of four malignant hepatocyte cell lines, 2) GABAA receptor mRNA expression in the same cell lines, and 3) effects of restoring malignant hepatocyte PDs to levels approximating those of res...

Parkinson's disease (PD) is characterized by both motor and nonmotor deficits. Among cardinal symptoms of this disorder, tremor the least responsive to dopamine replacement therapy often undertreated. Zuranolone (SAGE-217) an investigational oral neuroactive steroid (NAS) gamma-aminobutyric acid A (GABAA) receptor–positive allosteric modulator (PAM) that has been investigated for its safety eff...

An N-methyl-D-aspartate (NMDA)-independent form of long-term potentiation (LTP), which depends on postsynaptic, voltage-dependent calcium channels (VDCCs), has been demonstrated in area CA1 of hippocampus. GABA acting at GABAA receptors limits postsynaptic depolarization during LTP induction. Blockade of GABAA receptors should therefore enhance activation of postsynaptic VDCCs and facilitate th...

Some areas of the mammalian CNS, such as the retina, contain not one but two fast inhibitory neurotransmitter systems whose actions are mediated by GABA and glycine. Each inhibitory receptor system is encoded by a separate gene family and has a unique set of agonists and antagonists. Therefore, in rat retinal ganglion cells we were surprised to find that a single agent, extracellular glutathion...

Alterations of synaptic excitation induced by exposure to gamma-aminobutyric acid-A (GABAA) receptor antagonists were investigated employing tight-seal whole cell recording from single neurons or pairs of neurons in rat embryonic midbrain culture. Application of GABAA receptor antagonists led to sustained depolarizations followed by synchronous paroxysmal depolarization shifts (PDSs). PDSs indu...

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...

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...

Considerable evidence suggests that the neurotransmitter gamma-aminobutyric acid (GABA)-ergic system and pedunculopontine tegmentum (PPT) in the brain stem are critically involved in the regulation of rapid-eye-movement (REM) sleep. GABA and its various receptors are normally present in the PPT cholinergic cell compartment. The aim of this study was to identify the role of GABA and its receptor...

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...

Auditory steady-state auditory responses (ASSRs), in which the evoked potential entrains to stimulus frequency and phase, are reduced in magnitude in patients with schizophrenia, particularly at 40 Hz. While the neural mechanisms responsible for ASSR generation and its perturbation in schizophrenia are unknown, it has been hypothesized that the GABAA receptor subtype may have an important role....