Biomaterial Database

The effects of copper ions on glutamate receptors in cultured rat cortical neurons. 1996

T Weiser, and M Wienrich

Department of Biological Research, Boehringer Ingelheim KG, Germany. 1015742177@COMPUSERVE.COM

Copper plays an important role in the function of many physiological processes and can affect different neurotransmitter systems. In this study, we used the patch-clamp technique to investigate the effect of copper ions on glutamate receptors in cultured rat cortical neurons. Cu2+ inhibited (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors with an IC50 of 4.3 +/- 0.6 microM (with 100 microM kainate, holding potential -60 mV). The concentration-response could be best described by a two-site binding model. Moreover, copper reduced the efficacy of kainate at the AMPA receptor: in the presence of 30 microM Cu2+, the EC50 of kainate was shifted from 100.3 +/- 2.0 microM to 329.9 +/- 31.4 microM. The block by copper ions was not use-dependent. Complete recovery only occurred after the application of a high agonist concentration, or in the presence of the antioxidant dithiotreitol (DTT). A high concentration of histidine, a physiological ligand for Cu2+, did not augment the recovery. The kinetics of block were compared to those induced by 2,3-dihydro-6-nitro-7-sulfamoyl-benz(F)quinoxaline (NBQX), a well-described competitive antagonist of AMPA receptors. The onset, as well as the offset of block by NBQX could be well approximated by single exponential functions with time constants of 0.28 +/- 0.02 and 0.87 +/- 0.09 s, respectively. Within seconds of wash-out of the antagonist, the response to kainate completely recovered. The kinetics of copper block were more complex: the block developed more slowly, and the onset, as well as the offset could be described by two exponential functions with quite different time constants (tau(on1), 0.8 +/- 0.13 s; tau(on2), 8.32 +/- 1.13 s; tau(off1), 0.17 +/- 0.01 s; tau(off2), 69 +/- 36.3 s). In addition to the described effects, Cu2+ also blocked currents induced by the application of N-methyl-D-aspartate (IC50: 15.0 +/- 2.6 microM with 50 microM NMDA). Based on these findings, a modulatory role of copper ions on the neurotransmission by excitatory amino acids is discussed.

UI	MeSH Term	Description	Entries
D007608	Kainic Acid	(2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose.	Digenic Acid,Kainate,Acid, Digenic,Acid, Kainic
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D002540	Cerebral Cortex	The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.	Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D003300	Copper	A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.	Copper-63,Copper 63
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D017470	Receptors, Glutamate	Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells. Glutamate receptors include ionotropic receptors (AMPA, kainate, and N-methyl-D-aspartate receptors), which directly control ion channels, and metabotropic receptors which act through second messenger systems. Glutamate receptors are the most common mediators of fast excitatory synaptic transmission in the central nervous system. They have also been implicated in the mechanisms of memory and of many diseases.	Excitatory Amino Acid Receptors,Glutamate Receptors,Receptors, Excitatory Amino Acid,Excitatory Amino Acid Receptor,Glutamate Receptor,Receptor, Glutamate
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus