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The Journal of Neuroscience, May 24, 2006, 26(21):5750-5755; doi:10.1523/JNEUROSCI.0301-06.2006

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Brief Communications
External Ions Are Coactivators of Kainate Receptors

Adrian Y. C. Wong, Anne-Marie L. Fay, and Derek Bowie

Department of Pharmacology and Therapeutics, McGill University, Montreal, Québec, Canada H3A 1Y6

Correspondence should be addressed to Dr. Derek Bowie, Department of Pharmacology and Therapeutics, McIntyre Medical Sciences Building, Room 1317, McGill University, 3655 Promenade Sir William Osler, Montreal, Québec, Canada H3A 1Y6. Email: derek.bowie{at}mcgill.ca

The activation of ligand-gated ion channels is thought to depend solely on the binding of chemical neurotransmitters. In this study, we demonstrate that kainate (KA) ionotropic glutamate receptors (iGluRs) require not only the neurotransmitter L-glutamate (L-Glu) but also external sodium and chloride ions for activation. Removal of external ions traps KA receptors (KARs) in a novel inactive state that binds L-Glu with picomolar affinity. Moreover, occupancy of KARs by L-Glu precludes external ion binding, demonstrating crosstalk between ligand- and ion-binding sites. AMPA iGluRs function normally in the absence of external ions, revealing that even closely related iGluR subfamilies operate by distinct gating mechanisms. This behavior is interchangeable via a single amino acid residue that operates as a molecular switch to confer AMPA receptor behavior onto KARs. Our findings identify a novel allosteric site that singles out KARs from all other ligand-gated ion channels.

Key words: agonist; glutamate receptor; desensitization; gating; epilepsy; activation

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Received Jan. 23, 2006; revised April 10, 2006; accepted April 14, 2006.

Correspondence should be addressed to Dr. Derek Bowie, Department of Pharmacology and Therapeutics, McIntyre Medical Sciences Building, Room 1317, McGill University, 3655 Promenade Sir William Osler, Montreal, Québec, Canada H3A 1Y6. Email: derek.bowie{at}mcgill.ca

This article has been cited by other articles:

				A. Y. C. Wong, D. M. MacLean, and D. Bowie Na+/Cl- Dipole Couples Agonist Binding to Kainate Receptor Activation J. Neurosci., June 20, 2007; 27(25): 6800 - 6809. [Abstract] [Full Text] [PDF]

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