Cysteine substitutions define etomidate binding and gating linkages in the α-M1 domain of γγ-aminobutyric acid type A (GABAA) receptors

Abstract

Background: Etomidate induces anesthesia via intersubunit transmembrane sites in GABAA receptors. Results: In receptors engineered withα-M1 domain cysteines,GABAaccelerates modification. Etomidate inhibits modification at three positions. Conclusion: Etomidate contacts a subdomain of α-M1 linked to channel gating, consistent with in silico model docking. Significance: We identify new structures that both bind anesthetic and modulate channel gating through rearrangement. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.