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© Marie Prévost, Institut Pasteur
Image of a portion of a Xenopus oocyte expressing a channel receptor.
Publication : The Journal of physiology

The dual-gate model for pentameric ligand-gated ion channels activation and desensitization

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of physiology - 27 Feb 2018

Gielen M, Corringer PJ

Link to Pubmed [PMID] – 29484660

J. Physiol. (Lond.) 2018 Feb;

Pentameric ligand-gated ion channels (pLGICs) mediate fast neurotransmission in the nervous system. Their dysfunction is associated with psychiatric, neurological and neurodegenerative disorders such as schizophrenia, epilepsy and Alzheimer’s disease. Understanding their biophysical and pharmacological properties, both at the functional and structural levels, thus holds many therapeutic promises. In addition to their agonist-elicited activation, most pLGICs display another key allosteric property, namely desensitization, in which they enter a shut state refractory to activation upon sustained agonist binding. While the activation mechanisms of several pLGICs have been revealed at near-atomic resolution, the structural foundation of desensitization has long remained elusive. Recent structural and functional data now suggest that the activation and desensitization gates are distinct, and are located at both sides of the ion channel. Such a “dual gate mechanism” accounts for the marked allosteric effects of channel blockers, a feature illustrated herein by theoretical kinetics simulations. Comparison with other classes of ligand- and voltage-gated ion channels show that this dual gate mechanism emerges as a common theme for the desensitization and inactivation properties of structurally unrelated ion channels. This article is protected by copyright. All rights reserved.

https://www.ncbi.nlm.nih.gov/pubmed/29484660