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

Research output: Contribution to journalArticlepeer-review

Abstract

Neurosteroids are endogenous modulators of GABAA receptors that mediate anxiety, pain, mood and arousal. The 3-hydroxyl epimers, allopregnanolone (3α-OH) and epi-allopregnanolone (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.

Original languageEnglish
Pages (from-to)886-890
Number of pages5
JournalCurrent Neuropharmacology
Volume20
Issue number5
DOIs
StatePublished - May 2022

Keywords

  • affinity labeling
  • desensitization
  • GABA receptors
  • ion channels
  • Neurosteroids
  • structural biology

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