ArticleAnesthesiology2015
Inhalational anesthetics disrupt postsynaptic density protein-95, Drosophila disc large tumor suppressor, and zonula occludens-1 domain protein interactions critical to action of several excitatory receptor channels related to anesthesia.
Article in Anesthesiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Disruption of Extracellular Signal-Regulated Kinase Partially Mediates Neonatal Isoflurane Anesthesia-Induced Changes in Dendritic Spines and Cognitive Function in Juvenile Mice.International journal of molecular sciences · 2025Article
- Article
- Differential Effects of Sevoflurane Exposure on Long-Term Fear Memory in Neonatal and Adult Rats.Molecular neurobiology · 2022Article
- Neonatal Isoflurane Anesthesia or Disruption of Postsynaptic Density-95 Protein Interactions Change Dendritic Spine Densities and Cognitive Function in Juvenile Mice.Anesthesiology · 2020Article
- Transcriptional changes in response to ketamine ester-analogs SN 35210 and SN 35563 in the rat brain.BMC genomics · 2019Article
- Effects of Branched-Chain Amino Acid Supplementation on Spontaneous Seizures and Neuronal Viability in a Model of Mesial Temporal Lobe Epilepsy.Journal of neurosurgical anesthesiology · 2019Article
- Nitric Oxide Donor Prevents Neonatal Isoflurane-induced Impairments in Synaptic Plasticity and Memory.Anesthesiology · 2019Article
- The actions of volatile anesthetics: a new perspective.Acta crystallographica. Section D, Structural biology · 2018Review
- The Regulation of GluN2A by Endogenous and Exogenous Regulators in the Central Nervous System.Cellular and molecular neurobiology · 2017Review
- Molecular Mechanisms of Anesthetic Neurotoxicity: A Review of the Current Literature.Journal of neurosurgical anesthesiology · 2016Review
- Sensitivity to isoflurane anesthesia increases in autism spectrum disorder Shank3Neurotoxicology and teratologyArticle
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe authors have shown previously that inhaled anesthetics disrupt the interaction between the second postsynaptic density protein-95, Drosophila disc large tumor suppressor, and zonula occludens-1 (PDZ) domain of postsynaptic density protein-95 (PSD-95) and the C-terminus of N-methyl-D-aspartate receptor subunits NR2A and NR2B. The study data indicate that PDZ domains may serve as a molecular target for inhaled anesthetics. However, the underlying molecular mechanisms remain to be illustrated.
methodsGlutathione S-transferase pull-down assay, coimmunoprecipitation, and yeast two-hybrid analysis were used to assess PDZ domain-mediated protein-protein interactions in different conditions. Nuclear magnetic resonance spectroscopy was used to investigate isoflurane-induced chemical shift changes in the PDZ1-3 domains of PSD-95. A surface plasmon resonance-based BIAcore (Sweden) assay was used to examine the ability of isoflurane to inhibit the PDZ domain-mediated protein-protein interactions in real time.
resultsHalothane and isoflurane dose-dependently inhibited PDZ domain-mediated interactions between PSD-95 and Shaker-type potassium channel Kv1.4 and between α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluA2 and its interacting proteins-glutamate receptor-interacting protein or protein interacting with c kinase 1. However, halothane and isoflurane had no effect on PDZ domain-mediated interactions between γ-aminobutyric acid type B receptor and its interacting proteins. The inhaled anesthetic isoflurane mostly affected the residues close to or in the peptide-binding groove of PSD-95 PDZ1 and PDZ2 (especially PDZ2), while barely affecting the peptide-binding groove of PSD-95 PDZ3.
conclusionThese results suggest that inhaled anesthetics interfere with PDZ domain-mediated protein-protein interactions at several receptors important to neuronal excitation, anesthesia, and pain processing.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.