GABA(A) receptors as molecular targets of general anesthetics: identification of binding sites provides clues to allosteric modulation.

ABSTRACT:

Purpose

The purpose of this review is to summarize current knowledge of detailed biochemical evidence for the role of γ-aminobutyric acid type A receptors (GABA(A)-Rs) in the mechanisms of general anesthesia.

Principal findings

With the knowledge that all general anesthetics positively modulate GABA(A)-R-mediated inhibitory transmission, site-directed mutagenesis comparing sequences of GABA(A)-R subunits of varying sensitivity led to identification of amino acid residues in the transmembrane domain that are critical for the drug actions in vitro. Using a photo incorporable analogue of the general anesthetic, R(+)etomidate, we identified two transmembrane amino acids that were affinity labelled in purified bovine brain GABA(A)-R. Homology protein structural modelling position

SUBMITTER: Olsen RW 

PROVIDER: S-EPMC3033524 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature