External anions and cations distinguish between AMPA and kainate receptor gating mechanisms
- PMID: 11897844
- PMCID: PMC2290172
- DOI: 10.1113/jphysiol.2001.013407
External anions and cations distinguish between AMPA and kainate receptor gating mechanisms
Abstract
Experiments were designed to examine if ion-flow through alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic acid (AMPA) or kainate receptors interferes with protein structures associated with the gating machinery. Gating was studied using ultra-fast drug perfusion of outside-out patches containing rat GluR-A or GluR6 subunits excised from transfected human embryonic kidney cells. Deactivation rates of GluR6 kainate receptors observed following brief L-glutamate (10 mM Glu, 1 ms) applications differed by two to threefold in high (405 mM symmetrical Na(+), tau(decay) = 2.7 ms at -100 mV) and low ionic strength (55 mM, tau(decay) = 1.1 ms) solutions. In comparison, GluR-A AMPA receptors were much less sensitive. Ion effects on GluR6 receptors did not reflect surface potential screening or ion-agonist competition at the agonist-binding site since deactivation rates were slower in high ionic strength solutions. Moreover, the apparent agonist affinity did not decrease with increasing ionic strength (e.g. 55 mM, EC(50) = 110 microM vs. 405 mM, EC(50) = 61 microM). GluR6 responses were strongly dependent on ions present on the external, but not the internal, side of the plasma membrane. Decay kinetics was regulated by the type of ion present suggesting that the chemical nature of the solution, not its ionic strength, governed channel behaviour. Both external anions and cations modulated the amplitude and decay kinetics of GluR6 responses in a concomitant manner. AMPA receptor responses recorded in identical ionic conditions did not exhibit this behaviour. These results identify a novel mechanism that distinguishes AMPA and kainate receptors. External ions regulate the gating machinery of kainate receptors through an allosteric mechanism that involves both anions and cations.
Figures






Similar articles
-
Dendritic and somatic glutamate receptor channels in rat cerebellar Purkinje cells.J Physiol. 1997 May 15;501 ( Pt 1)(Pt 1):77-95. doi: 10.1111/j.1469-7793.1997.077bo.x. J Physiol. 1997. PMID: 9174996 Free PMC article.
-
Dominance of the lurcher mutation in heteromeric kainate and AMPA receptor channels.Eur J Neurosci. 2001 Sep;14(5):861-8. doi: 10.1046/j.0953-816x.2001.01705.x. Eur J Neurosci. 2001. PMID: 11576190
-
A role for extracellular Na+ in the channel gating of native and recombinant kainate receptors.J Neurosci. 2003 Sep 24;23(25):8641-8. doi: 10.1523/JNEUROSCI.23-25-08641.2003. J Neurosci. 2003. PMID: 14507963 Free PMC article.
-
Gating and permeation of kainate receptors: differences unveiled.Trends Pharmacol Sci. 2010 Nov;31(11):516-22. doi: 10.1016/j.tips.2010.08.004. Epub 2010 Sep 16. Trends Pharmacol Sci. 2010. PMID: 20850188 Review.
-
Pharmacology of AMPA/kainate receptor ligands and their therapeutic potential in neurological and psychiatric disorders.Drugs. 2000 Jan;59(1):33-78. doi: 10.2165/00003495-200059010-00004. Drugs. 2000. PMID: 10718099 Review.
Cited by
-
Structure of the kainate receptor subunit GluR6 agonist-binding domain complexed with domoic acid.Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1708-13. doi: 10.1073/pnas.0409573102. Epub 2005 Jan 26. Proc Natl Acad Sci U S A. 2005. PMID: 15677325 Free PMC article.
-
The structural arrangement at intersubunit interfaces in homomeric kainate receptors.Sci Rep. 2019 May 6;9(1):6969. doi: 10.1038/s41598-019-43360-x. Sci Rep. 2019. PMID: 31061516 Free PMC article.
-
Novel Functional Properties of Drosophila CNS Glutamate Receptors.Neuron. 2016 Dec 7;92(5):1036-1048. doi: 10.1016/j.neuron.2016.10.058. Epub 2016 Nov 23. Neuron. 2016. PMID: 27889096 Free PMC article.
-
Defining the structural relationship between kainate-receptor deactivation and desensitization.Nat Struct Mol Biol. 2013 Sep;20(9):1054-61. doi: 10.1038/nsmb.2654. Epub 2013 Aug 18. Nat Struct Mol Biol. 2013. PMID: 23955023 Free PMC article.
-
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacol Rev. 2021 Oct;73(4):298-487. doi: 10.1124/pharmrev.120.000131. Pharmacol Rev. 2021. PMID: 34753794 Free PMC article. Review.
References
-
- Antonov SM, Gmiro VE, Johnson JW. Binding sites for permeant ions in the channel of NMDA receptors and their effects on channel block. Nature Neuroscience. 1998;1:451–456. - PubMed
-
- Arai A, Silberg J, Kessler M, Lynch G. Effect of thiocyanate on AMPA receptor mediated responses in excised patches and hippocampal slices. Neuroscience. 1995;66:815–827. - PubMed
-
- Armstrong N, Gouaux E. Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core. Neuron. 2000;28:165–181. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources