{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:11:15Z","timestamp":1793149875160,"version":"4.5.0"},"reference-count":93,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["NS112292"],"award-info":[{"award-number":["NS112292"]}]},{"name":"NIH","award":["DA044121"],"award-info":[{"award-number":["DA044121"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>In physiological conditions, the intracellular chloride concentration is much lower than the extracellular. As GABAA channels are permeable to anions, the reversal potential of GABAA is very close to that of Cl\u2212, which is the most abundant free anion in the intra- and extracellular spaces. Intracellular chloride is regulated by the activity ratio of NKCC1 and KCC2, two chloride-cation cotransporters that import and export Cl\u2212, respectively. Due to the closeness between GABAA reversal potential and the value of the resting membrane potential in most neurons, small changes in intracellular chloride have a major functional impact, which makes GABAA a uniquely flexible signaling system. In most neurons of the adult brain, the GABAA reversal potential is slightly more negative than the resting membrane potential, which makes GABAA hyperpolarizing. Alterations in GABAA reversal potential are a common feature in numerous conditions as they are the consequence of an imbalance in the NKCC1-KCC2 activity ratio. In most conditions (including Alzheimer\u2019s disease, schizophrenia, and Down\u2019s syndrome), GABAA becomes depolarizing, which causes network desynchronization and behavioral impairment. In other conditions (neonatal inflammation and neuropathic pain), however, GABAA reversal potential becomes hypernegative, which affects behavior through a potent circuit deactivation.<\/jats:p>","DOI":"10.3390\/life14010143","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T03:33:41Z","timestamp":1705635221000},"page":"143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Bidirectional Regulation of GABAA Reversal Potential in the Adult Brain: Physiological and Pathological Implications"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9270-335X","authenticated-orcid":false,"given":"Haram R.","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Feinberg School of Medicine, Northwestern University, 300 E. Superior, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9648-2918","authenticated-orcid":false,"given":"Marco","family":"Martina","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Feinberg School of Medicine, Northwestern University, 300 E. Superior, Chicago, IL 60611, USA"},{"name":"Department of Psychiatry, Feinberg School of Medicine, Northwestern University, 300 E. Superior, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.neuron.2009.04.027","article-title":"Instantaneous modulation of gamma oscillation frequency by balancing excitation with inhibition","volume":"62","author":"Atallah","year":"2009","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nature10360","article-title":"Neocortical excitation\/inhibition balance in information processing and social dysfunction","volume":"477","author":"Yizhar","year":"2011","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"23176","DOI":"10.1038\/srep23176","article-title":"Dynamic Balance of Excitation and Inhibition in Human and Monkey Neocortex","volume":"6","author":"Dehghani","year":"2016","journal-title":"Sci. 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