REVIEW article
Front. Pharmacol.
Sec. Pharmacology of Ion Channels and Channelopathies
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1662316
This article is part of the Research TopicNew Insights into Ionotropic Glutamate Receptor Structure and Function in Health and DiseaseView all 4 articles
Structure and gating of kainate receptors
Provisionally accepted
- Columbia University, New York City, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Ionotropic glutamate receptors (iGluRs) are crucial for fast excitatory neurotransmission in the mammalian central nervous system (CNS). Kainate receptors (KARs), a subclass of iGluRs, are tetrameric, ligand-gated ion channels that play key modulatory roles at both pre-and postsynaptic sites within neuronal circuits and in the regulation of synaptic plasticity. KARs are composed of GluK1-GluK5 subunits, with subunits GluK1-GluK3 forming functional homo-and heteromeric channels, while GluK4-GluK5 assemble as obligate heteromers, partnering with subunits GluK1-GluK3. Over the past two decades, numerous homomeric and heteromeric structures of isolated domains and the full-length receptor have been solved in various functional states, providing detailed descriptions of functional mechanisms, thereby addressing several longstanding questions in the field of KAR biology. These studies revealed overall structural similarity of KARs with other iGluRs, particularly AMPA receptors in the closed and activated states, and the agonist-bound non-conducting state adopting a conformation which is different from other iGluRs. This review highlights recent structural insights into gating and pharmacological regulation of KARs, offering deeper understanding of their roles in synaptic transmission and neuronal signaling.
Keywords: kainate receptor, cryo-EM, Gating mechanism, Channel blockers, allostericmodulators, Neto1/2
Received: 09 Jul 2025; Accepted: 06 Oct 2025.
Copyright: © 2025 Gangwar, Yelshanskaya, Yen, Newton and Sobolevsky. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Shanti Pal Gangwar, sg3757@cumc.columbia.edu
Alexander I Sobolevsky, as4005@cumc.columbia.edu
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.