• Stuart A Forman.
• Department of Anesthesia Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. saforman@partners.org
• Curr Opin Anaesthesiol. 2012 Aug 1;25(4):411-8.

Purpose Of ReviewFormal Monod-Wyman-Changeux allosteric mechanisms have proven valuable in framing research on the mechanism of etomidate action on its major molecular targets, γ-aminobutyric acid type A (GABAA) receptors. However, the mathematical formalism of these mechanisms makes them difficult to comprehend.Recent FindingsWe illustrate how allosteric models represent shifting equilibria between various functional receptor states (closed versus open) and how co-agonism can be readily understood as simply addition of gating energy associated with occupation of distinct agonist sites. We use these models to illustrate how the functional effects of a point mutation, α1M236W, in GABAA receptors can be translated into an allosteric model phenotype.SummaryAllosteric co-agonism provides a robust framework for design and interpretation of structure-function experiments aimed at understanding where and how etomidate affects its GABAA receptor target molecules.

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