Effect of RNA Editing and Subunit Co-assembly Single-channel Properties of Recombinant Kainate Receptors

Overview

Journal J Physiol

Specialty Physiology

Date 1996 Apr 1

PMID 8730589

Citations 69

Authors

G T Swanson

D Feldmeyer

M Kaneda

S G Cull-Candy

Affiliations

Soon will be listed here.

Abstract

1. Patch-clamp methods have been used to examine single-channel properties of recombinant GluR5 and GluR6 kainate-preferring glutamate receptors which differ in a single amino acid residue as a result of RNA editing at the Q/R (glutamine/arginine) site. Subunits were expressed alone or in combination with the high-affinity kainate receptor subunit KA - 2 in transfected human embryonic kidney (HEK-293) cells. 2. In outside-out patches, unedited homomeric GluR6(Q) receptors exhibited directly resolved domoate-activated single-channel conductances of 8, 15 and 25 pS. Variance analysis of GluR6(Q) responses gave a mean conductance of 5.4 pS, while the edited isoform GluR6(R) had an unusually low channel conductance (225 fS). 3. Homomeric channels composed of GluR5(Q) subunits exhibited three conductance states of 5, 9 and 14 pS characterized by prolonged burst activations in the presence of domoate. In contrast, the GluR5(R) subunit, which has not previously been reported to form functional homomeric receptors, had an extremely low conductance (< 200 fS). 4. Heteromeric GluR6(Q)/KA-2 kainate receptors gave single-channel events indistinguishible from homomeric GluR6(Q) channels. Conversely, openings produced by GluR5(Q)KA-2 and GluR5(Q) receptors differed from each other in their kinetic properties. The primary effect of co-expression of KA-2 with GluR5(Q) was a dramatic shortening in channel burst length. 5. Spectral and variance analyses were used to estimate mean single-channel conductances of heteromeric edited receptor-channels; channel conductances were 950 fS for GluR5(R)KA-2 receptors and 700 fS for GluR6(R)/KA-2 receptors. Both receptor types had significantly higher conductances than the respective homomeric channels, GluR5(R) and GluR6(R). 6. We conclude that Q/R site editing dramatically reduces single-channel conductance. Furthermore, we find similarity between the kainate receptor-channels described in sensory neurones and the recombinant GluR5(Q) homomeric channel. Characterization of recombinant single-channel properties could therefore aid identification of the native kainate receptors.

Citing Articles

Calcium-permeable AMPA and kainate receptors of GABAergic neurons.

Zinchenko V, Dolgacheva L, Tuleukhanov S Biophys Rev. 2024; 16(2):165-171.

PMID: 38737208 PMC: 11078900. DOI: 10.1007/s12551-024-01184-8.

Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age.

Brunetti V, Soda T, Berra-Romani R, De Sarro G, Guerra G, Scarpellino G Biomedicines. 2024; 12(4).

PMID: 38672234 PMC: 11048239. DOI: 10.3390/biomedicines12040880.

RNA editing of ion channels and receptors in physiology and neurological disorders.

Zhai J, Koh J, Soong T Oxf Open Neurosci. 2024; 1:kvac010.

PMID: 38596706 PMC: 11003377. DOI: 10.1093/oons/kvac010.

GluK2 Q/R editing regulates kainate receptor signaling and long-term potentiation of AMPA receptors.

Nair J, Wilkinson K, Yucel B, Mulle C, Vissel B, Mellor J iScience. 2023; 26(10):107708.

PMID: 37720087 PMC: 10504484. DOI: 10.1016/j.isci.2023.107708.

Structure, Function, and Regulation of the Kainate Receptor.

Dhingra S, Yadav J, Kumar J Subcell Biochem. 2022; 99:317-350.

PMID: 36151381 DOI: 10.1007/978-3-031-00793-4_10.

References

Cull-Candy S, Ogden D . Ion channels activated by L-glutamate and GABA in cultured cerebellar neurons of the rat. Proc R Soc Lond B Biol Sci. 1985; 224(1236):367-73. DOI: 10.1098/rspb.1985.0038. View

Jahr C, Stevens C . Glutamate activates multiple single channel conductances in hippocampal neurons. Nature. 1987; 325(6104):522-5. DOI: 10.1038/325522a0. View

Cull-Candy S, Usowicz M . Multiple-conductance channels activated by excitatory amino acids in cerebellar neurons. Nature. 1987; 325(6104):525-8. DOI: 10.1038/325525a0. View

Ascher P, Nowak L . Quisqualate- and kainate-activated channels in mouse central neurones in culture. J Physiol. 1988; 399:227-45. PMC: 1191661. DOI: 10.1113/jphysiol.1988.sp017077. View

Cull-Candy S, Howe J, Ogden D . Noise and single channels activated by excitatory amino acids in rat cerebellar granule neurones. J Physiol. 1988; 400:189-222. PMC: 1191804. DOI: 10.1113/jphysiol.1988.sp017117. View

Huettner J . Glutamate receptor channels in rat DRG neurons: activation by kainate and quisqualate and blockade of desensitization by Con A. Neuron. 1990; 5(3):255-66. DOI: 10.1016/0896-6273(90)90163-a. View

Bettler B, Boulter J, Hermans-Borgmeyer I, Deneris E, Moll C, Borgmeyer U . Cloning of a novel glutamate receptor subunit, GluR5: expression in the nervous system during development. Neuron. 1990; 5(5):583-95. DOI: 10.1016/0896-6273(90)90213-y. View

Egebjerg J, Bettler B, Hermans-Borgmeyer I, Heinemann S . Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not AMPA. Nature. 1991; 351(6329):745-8. DOI: 10.1038/351745a0. View

Newland C, Colquhoun D, Cull-Candy S . Single channels activated by high concentrations of GABA in superior cervical ganglion neurones of the rat. J Physiol. 1991; 432:203-33. PMC: 1181323. DOI: 10.1113/jphysiol.1991.sp018382. View

10.

Hume R, Dingledine R, Heinemann S . Identification of a site in glutamate receptor subunits that controls calcium permeability. Science. 1991; 253(5023):1028-31. DOI: 10.1126/science.1653450. View

11.

Sommer B, Kohler M, Sprengel R, Seeburg P . RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell. 1991; 67(1):11-9. DOI: 10.1016/0092-8674(91)90568-j. View

12.

Burnashev N, Monyer H, Seeburg P, Sakmann B . Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit. Neuron. 1992; 8(1):189-98. DOI: 10.1016/0896-6273(92)90120-3. View

13.

Sommer B, Burnashev N, Verdoorn T, Keinanen K, Sakmann B, Seeburg P . A glutamate receptor channel with high affinity for domoate and kainate. EMBO J. 1992; 11(4):1651-6. PMC: 556615. DOI: 10.1002/j.1460-2075.1992.tb05211.x. View

14.

Herb A, Burnashev N, Werner P, Sakmann B, Wisden W, Seeburg P . The KA-2 subunit of excitatory amino acid receptors shows widespread expression in brain and forms ion channels with distantly related subunits. Neuron. 1992; 8(4):775-85. DOI: 10.1016/0896-6273(92)90098-x. View

15.

Lambolez B, Audinat E, Bochet P, Crepel F, Rossier J . AMPA receptor subunits expressed by single Purkinje cells. Neuron. 1992; 9(2):247-58. DOI: 10.1016/0896-6273(92)90164-9. View

16.

Egebjerg J, Heinemann S . Ca2+ permeability of unedited and edited versions of the kainate selective glutamate receptor GluR6. Proc Natl Acad Sci U S A. 1993; 90(2):755-9. PMC: 45744. DOI: 10.1073/pnas.90.2.755. View

17.

Raymond L, Blackstone C, Huganir R . Phosphorylation and modulation of recombinant GluR6 glutamate receptors by cAMP-dependent protein kinase. Nature. 1993; 361(6413):637-41. DOI: 10.1038/361637a0. View

18.

Kohler M, Burnashev N, Sakmann B, Seeburg P . Determinants of Ca2+ permeability in both TM1 and TM2 of high affinity kainate receptor channels: diversity by RNA editing. Neuron. 1993; 10(3):491-500. DOI: 10.1016/0896-6273(93)90336-p. View

19.

Huntley G, ROGERS S, Moran T, Janssen W, Archin N, Vickers J . Selective distribution of kainate receptor subunit immunoreactivity in monkey neocortex revealed by a monoclonal antibody that recognizes glutamate receptor subunits GluR5/6/7. J Neurosci. 1993; 13(7):2965-81. PMC: 6576683. View

20.

Mackler S, Eberwine J . Diversity of glutamate receptor subunit mRNA expression within live hippocampal CA1 neurons. Mol Pharmacol. 1993; 44(2):308-15. View