GABA is the principal inhibitory neurotransmitter in the CNS and acts via GABA(A) and GABA(B) receptors. Recently, a novel form of GABA(A) receptor-mediated inhibition, termed "tonic" inhibition, has been described. Whereas synaptic GABA(A) receptors underlie classical "phasic" GABA(A) receptor-mediated inhibition (inhibitory postsynaptic currents), tonic GABA(A) receptor-mediated inhibition results from the activation of extrasynaptic receptors by low concentrations of ambient GABA. Extrasynaptic GABA(A) receptors are composed of receptor subunits that convey biophysical properties ideally suited to the generation of persistent inhibition and are pharmacologically and functionally distinct from their synaptic counterparts. This mini-symposium review highlights ongoing work examining the properties of recombinant and native extrasynaptic GABA(A) receptors and their preferential targeting by endogenous and clinically relevant agents. In addition, it emphasizes the important role of extrasynaptic GABA(A) receptors in GABAergic inhibition throughout the CNS and identifies them as a major player in both physiological and pathophysiological processes.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784229 | PMC |
| http://dx.doi.org/10.1523/JNEUROSCI.3340-09.2009 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Bridging the gap: The endocannabinoid system as a functional fulcrum for benzodiazepines in a novel frontier of anxiety pharmacotherapy.
Pharmacol Ther
January 2025
Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:
While benzodiazepines have been a mainstay of the pharmacotherapy of anxiety disorders, their short-term efficacy and risk of abuse have driven the exploration of alternative treatment approaches. The endocannabinoid (eCB) system has emerged as a key modulator of anxiety-related processes, with evidence suggesting dynamic interactions between the eCB system and the GABAergic system, the primary target of benzodiazepines. According to the existing literature, the activation of the cannabinoid receptors has been shown to exert anxiolytic effects, while their blockade or genetic deletion results in heightened anxiety-like responses.
View Article and Find Full Text PDFAlpha6-containing GABA receptors - Novel targets for the treatment of schizophrenia.
Pharmacol Res
January 2025
Center for Brain Research, Department of Molecular Neurosciences, Medical University Vienna, Vienna, Austria. Electronic address:
α6-containing GABA receptors (α6GABARs) are strongly expressed in cerebellar granule cells and are of central importance for cerebellar functions. The cerebellum not only is involved in regulation of motor activity, but also in regulation of thought, cognition, emotion, language, and social behavior. Activation of α6GABARs enhances the precision of sensory inputs, enables rapid and coordinated movement and adequate responses to the environment, and protects the brain from information overflow.
View Article and Find Full Text PDFResolving native GABA receptor structures from the human brain.
Nature
January 2025
Department of Neurobiology, University of California San Diego, La Jolla, CA, USA.
Type A GABA (γ-aminobutyric acid) receptors (GABA receptors) mediate most fast inhibitory signalling in the brain and are targets for drugs that treat epilepsy, anxiety, depression and insomnia and for anaesthetics. These receptors comprise a complex array of 19 related subunits, which form pentameric ligand-gated ion channels. The composition and structure of native GABA receptors in the human brain have been inferred from subunit localization in tissue, functional measurements and structural analysis from recombinant expression and in mice.
View Article and Find Full Text PDFGABA mitigates mitochondrial apoptosis induced by high temperature stress in the Pacific oyster (Crassostrea gigas).
Mol Biol Rep
January 2025
College of Life Sciences, Liaoning Normal University, Dalian, Liaoning, 116029, China.
Background: High temperature is a critical environmental factor leading to mass mortality in oyster aquaculture in China. Recent advancements highlight the physiological regulation function of γ-aminobutyric acid (GABA) in the adaptation of environmental stress.
Methods And Results: This study examined the physiological responses of the Pacific oyster (Crassostrea gigas) upon high temperature exposure, focusing on the histopathological changes in gill, the GABA concentration, the mRNA expression and activities of apoptosis-related genes.
Multifactorial approach is needed to unravel the maturation phases of human neurons derived from induced pluripotent stem cells.
Sci Rep
January 2025
Department of Physiology and Neurobiology, Institute of Biology, Eötvös Loránd University, Pázmány Péter Sétány 1/C, Budapest, 1117, Hungary.
Neurons derived from induced pluripotent stem cells (h-iPSC-Ns) provide an invaluable model for studying the physiological aspects of human neuronal development under healthy and pathological conditions. However, multiple studies have demonstrated that h-iPSC-Ns exhibit a high degree of functional and epigenetic diversity. Due to the imprecise characterization and significant variation among the currently available maturation protocols, it is essential to establish a set of criteria to standardize models and accurately characterize and define the developmental properties of human neurons derived from iPSCs.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!