{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:53:29Z","timestamp":1791316409321,"version":"4.3.1"},"reference-count":656,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,10,12]],"date-time":"2004-10-12T00:00:00Z","timestamp":1097539200000},"content-version":"vor","delay-in-days":3268,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Synapse"],"published-print":{"date-parts":[[1995,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The \u03b3\u2010aminobutyric acid type A (GABA<jats:sub>A<\/jats:sub>) receptor represents an elementary switching mechanism integral to the functioning of the central nervous system and a locus for the action of many mood\u2010and emotion\u2010altering agents such as benzodiazepines, barbiturates, steroids, and alcohol. Anxiety, sleep disorders, and convulsive disorders have been effectively treated with therapeutic agents that enhance the action of GABA at the GABA<jats:sub>A<\/jats:sub> receptor or increase the concentration of GABA in nervous tissue. The GABA<jats:sub>A<\/jats:sub> receptor is a multimeric membrane\u2010spanning ligand\u2010gated ion channel that admits chloride upon binding of the neurotransmitter GABA and is modulated by many endogenous and therapeutically important agents. Since GABA is the major inhibitory neurotransmitter in the CNS, modulation of its response has profound implications for brain functioning. The GABA<jats:sub>A<\/jats:sub> receptor is virtually the only site of action for the centrally acting benzodiazepines, the most widely prescribed of the anti\u2010anxiety medications. 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 GABA<jats:sub>A<\/jats:sub> 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 GABA<jats:sub>A<\/jats:sub>, 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 (\u03b1l\u2010\u03b16, \u03b2l\u2010\u03b24, \u03b3l\u2010\u03b34,\u03b4, pl\u2010p2) and alternatively spliced variants contribute to the molecular architecture of the GABA<jats:sub>A<\/jats:sub> receptor. Mysteriously, certain preferred combinations of subunits, most notably the \u03b1l\u03b22\u03b32 arrangement, are widely codistributed, while the expression of other subunits, such as \u03b2l or \u03b16, is severely restricted to specific neurons in the hippocampal formation or cerebellar cortex. Nervous tissue has the capacity to exert control over receptor number, allosteric uncoupling, subunit mRNA levels, and posttranslational modifications.<\/jats:p>","DOI":"10.1002\/syn.890210302","type":"journal-article","created":{"date-parts":[[2004,12,31]],"date-time":"2004-12-31T22:26:39Z","timestamp":1104531999000},"page":"189-274","source":"Crossref","is-referenced-by-count":429,"title":["From ion currents to genomic analysis: Recent advances in GABA<sub>A<\/sub> receptor research"],"prefix":"10.1002","volume":"21","author":[{"given":"Lois E.","family":"Rabow","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelley J.","family":"Russek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Farb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,10,12]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"1414","article-title":"Modulation of the developing rat sympathetic GABAA receptor by Zn++ benzodiazepines, barbiturates and ethanol","volume":"267","author":"Aguayo L. 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