This review was presented at a symposium on Neurophysiology of inhibitory & excitatory amino acid receptors which took place at the 11th International Congress on Amino Acids, Peptides and Proteins, Vienna, on 3 August 2009.
Ion-dependent gating of kainate receptors
Article first published online: 4 JAN 2010
© 2010 The Author. Journal compilation © 2010 The Physiological Society
The Journal of Physiology
Volume 588, Issue 1, pages 67–81, January 2010
How to Cite
Bowie, D. (2010), Ion-dependent gating of kainate receptors. The Journal of Physiology, 588: 67–81. doi: 10.1113/jphysiol.2009.178863
- Issue published online: 4 JAN 2010
- Article first published online: 4 JAN 2010
- (Received 18 July 2009; accepted after revision 9 October 2009; first published online 12 October 2009)
Ligand-gated ion channels are an important class of signalling protein that depend on small chemical neurotransmitters such as acetylcholine, l-glutamate, glycine and γ-aminobutyrate for activation. Although numerous in number, neurotransmitter substances have always been thought to drive the receptor complex into the open state in much the same way and not rely substantially on other factors. However, recent work on kainate-type (KAR) ionotropic glutamate receptors (iGluRs) has identified an exception to this rule. Here, the activation process fails to occur unless external monovalent anions and cations are present. This absolute requirement of ions singles out KARs from all other ligand-gated ion channels, including closely related AMPA- and NMDA-type iGluR family members. The uniqueness of ion-dependent gating has earmarked this feature of KARs as a putative target for the development of selective ligands; a prospect all the more compelling with the recent elucidation of distinct anion and cation binding pockets. Despite these advances, much remains to be resolved. For example, it is still not clear how ion effects on KARs impacts glutamatergic transmission. I conclude by speculating that further analysis of ion-dependent gating may provide clues into how functionally diverse iGluRs families emerged by evolution. Consequently, ion-dependent gating of KARs looks set to continue to be a subject of topical inquiry well into the future.