Synaptic PDZ Domain-mediated Protein Interactions Are Disrupted by Inhalational Anesthetics* Academic Article uri icon

abstract

  • Anesthetics exert multiple effects on the central nervous system through altering synaptic transmission, but the mechanisms for this process are poorly understood. PDZ domain-mediated protein interactions play a central role in organizing signaling complexes around synaptic receptors for efficient signal transduction. We report here that clinically relevant concentrations of inhalational anesthetics dose-dependently and specifically inhibit the PDZ domain-mediated protein interaction between PSD-95 or PSD-93 and the N-methyl-d-aspartate receptor or neuronal nitric-oxide synthase. These inhibitory effects are immediate, potent, and reversible and occur at a hydrophobic peptide-binding groove on the surface of the second PDZ domain of PSD-95 in a manner relevant to anesthetic action. These findings reveal the PDZ domain as a new molecular target for inhalational anesthetics.

altmetric score

  • 3

author list (cited authors)

  • Fang, M., Tao, Y., He, F., Zhang, M., Levine, C. F., Mao, P., ... Johns, R. A.

citation count

  • 30

publication date

  • July 2003