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- Title
Intricacies of GABA A Receptor Function: The Critical Role of the β3 Subunit in Norm and Pathology.
- Authors
Menzikov, Sergey A.; Morozov, Sergey G.; Kubatiev, Aslan A.; Hernandez, Ciria C.
- Abstract
Neuronal intracellular chloride ([Cl−]i) is a key determinant in γ-aminobutyric acid type A (GABA)ergic signaling. γ-Aminobutyric acid type A receptors (GABAARs) mediate both inhibitory and excitatory neurotransmission, as the passive fluxes of Cl− and HCO3− via pores can be reversed by changes in the transmembrane concentration gradient of Cl−. The cation–chloride co-transporters (CCCs) are the primary systems for maintaining [Cl−]i homeostasis. However, despite extensive electrophysiological data obtained in vitro that are supported by a wide range of molecular biological studies on the expression patterns and properties of CCCs, the presence of ontogenetic changes in [Cl−]i—along with the consequent shift in GABA reversal potential—remain a subject of debate. Recent studies showed that the β3 subunit possesses properties of the P-type ATPase that participates in the ATP-consuming movement of Cl− via the receptor. Moreover, row studies have demonstrated that the β3 subunit is a key player in GABAAR performance and in the appearance of serious neurological disorders. In this review, we discuss the properties and driving forces of CCCs and Cl−, HCO3−ATPase in the maintenance of [Cl−]i homeostasis after changes in upcoming GABAAR function. Moreover, we discuss the contribution of the β3 subunit in the manifestation of epilepsy, autism, and other syndromes.
- Subjects
GABA receptors; GLYCINE receptors; CONCENTRATION gradient; NEUROLOGICAL disorders; PATHOLOGY; GABA
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 3, p1457
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms22031457