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Current Neuropharmacology

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ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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Perspective

Neurosteroid Modulation of GABAA Receptor Function by Independent Action at Multiple Specific Binding Sites

Author(s): Lei Wang, Douglas F. Covey, Gustav Akk and Alex S. Evers*

Volume 20, Issue 5, 2022

Published on: 01 March, 2022

Page: [886 - 890] Pages: 5

DOI: 10.2174/1570159X19666211202150041

Abstract

Neurosteroids are endogenous modulators of GABAA receptors that mediate anxiety, pain, mood and arousal. The 3-hydroxyl epimers, allopregnanolone (3α-OH) and epiallopregnanolone (3β-OH) are both prevalent in the mammalian brain and produce opposite effects on GABAA receptor function, acting as positive and negative allosteric modulators, respectively. This Perspective provides a model to explain the actions of 3α-OH and 3β-OH neurosteroids. The model is based on evidence that the neurosteroid epimers bind to an overlapping subset of specific sites on GABAA receptors, with their net functional effect on channel gating being the sum of their independent effects at each site.

Keywords: Neurosteroids, GABAA receptors, ion channels, affinity labeling, desensitization, structural biology.

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