Functional regulation of GABAA receptors in nervous system pathologies.
Inhibitory neurotransmission is primarily governed by γ-aminobutyric acid (GABA) type A receptors (GABAARs). GABAARs are heteropentameric ligand-gated channels formed by the combination of 19 possible subunits. GABAAR subunits are subject to multiple types of regulation, impacting the localization, properties, and function of assembled receptors. GABAARs mediate both phasic (synaptic) and tonic (extrasynaptic) inhibition. While the regulatory mechanisms governing synaptic receptors have begun to be defined, little is known about the regulation of extrasynaptic receptors. We examine the contributions of GABAARs to the pathogenesis of neurodevelopmental disorders, schizophrenia, depression, epilepsy, and stroke, with particular focus on extrasynaptic GABAARs. We suggest that extrasynaptic GABAARs are attractive targets for the treatment of these disorders, and that research should be focused on delineating the mechanisms that regulate extrasynaptic GABAARs, promoting new therapeutic approaches.
Department of Neuroscience, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA 02111, USA.
Rochelle M
RM
Hines
Paul A
PA
Davies
Stephen J
SJ
Moss
Jamie
J
Maguire
D000818:Animals; D006801:Humans; D009422:Nervous System Diseases / Q000378:metabolism* / Q000473:pathology*; D018079:Receptors, GABA / Q000145:classification / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism / Q000473:pathology
D018079:Receptors, GABA