NDLI: Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC

Content Provider	PubMed Central
Author	Chen, Qiang Kinde, Monica N. Arjunan, Palaniappa Wells, Marta M. Cohen, Aina E. Xu, Yan Tang, Pei
Copyright Year	2015
Abstract	Pentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics, but molecular mechanisms underlying anesthetic action remain debatable. We found that ELIC, a pLGIC from Erwinia chrysanthemi, can be functionally inhibited by isoflurane and other anesthetics. Structures of ELIC co-crystallized with isoflurane in the absence or presence of an agonist revealed double isoflurane occupancies inside the pore near T237(6′) and A244(13′). A pore-radius contraction near the extracellular entrance was observed upon isoflurane binding. Electrophysiology measurements with a single-point mutation at position 6′ or 13′ support the notion that binding at these sites renders isoflurane inhibition. Molecular dynamics simulations suggested that isoflurane binding was more stable in the resting than in a desensitized pore conformation. This study presents compelling evidence for a direct pore-binding mechanism of isoflurane inhibition, which has a general implication for inhibitory action of general anesthetics on pLGICs.
Related Links	http://dx.doi.org/10.1038/srep13833
Starting Page	13833
File Format	PDF
ISSN	20452322
e-ISSN	20452322
Journal	Scientific Reports
Volume Number	5
Language	English
Publisher	Nature Publishing Group
Publisher Date	2015-09-01
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Science and technology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC

Structural Basis of Alcohol Inhibition of the Pentameric Ligand-Gated Ion Channel ELIC

Inhibition of the Prokaryotic Pentameric Ligand-Gated Ion Channel ELIC by Divalent Cations (2012)

Pentameric ligand-gated ion channel ELIC is activated by GABA and modulated by benzodiazepines

Pore opening and closing of a pentameric ligand-gated ion channel

Isoflurane alters the structure and dynamics of glic (2011).

Crystal structures of a pentameric ligand-gated ion channel provide a mechanism for activation

Ligand Activation of the Prokaryotic Pentameric Ligand- Gated Ion Channel ELIC (2011)

Multisite Binding of a General Anesthetic to the Prokaryotic Pentameric Erwinia chrysanthemi Ligand-gated Ion Channel (ELIC)*

Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC

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Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC

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