Trace metals in the brain: allosteric modulators of ligand-gated receptor channels, the case of ATP-gated P2X receptors

Zinc and copper are indispensable trace metals for life with a recognized role as catalysts in enzyme actions. We now review evidence supporting the role of trace metals as novel allosteric modulators of ionotropic receptors: a new and fundamental physiological role for zinc and copper in neuronal a...

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Autores: Huidobro-Toro, J.P., Lorca, R.A., Coddou, C.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2008
País:Chile
Idioma:inglés
OAI Identifier:oai:repositorio.anid.cl:10533/236937
Acceso en línea:https://hdl.handle.net/10533/236937
Access Level:acceso abierto
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spelling Coddou, C.Lorca, R.A.Huidobro-Toro, J.P.200810.1007/s00249-007-0230-7https://hdl.handle.net/10533/236937http://purl.org/coar/access_right/c_abf2Trace metals in the brain: allosteric modulators of ligand-gated receptor channels, the case of ATP-gated P2X receptorsHuidobro-Toro, J.P.Lorca, R.A.Coddou, C.2019-12-18T18:14:22Z2022-07-07T21:58:40Z2019-12-18T18:14:22Z2022-07-07T21:58:40Z2008Zinc and copper are indispensable trace metals for life with a recognized role as catalysts in enzyme actions. We now review evidence supporting the role of trace metals as novel allosteric modulators of ionotropic receptors: a new and fundamental physiological role for zinc and copper in neuronal and brain excitability. The review is focussed on ionotropic receptor channels including nucleotide receptors, in particular the P2X receptor family. Since zinc and copper are stored within synaptic vesicles in selected brain regions, and released to the synaptic cleft upon electrical nerve ending depolarization, it is plausible that zinc and copper reach concentrations in the synapse that profoundly affect ligand-gated ionic channels, including the ATP-gated currents of P2X receptors. The identification of key P2X receptor amino acids that act as ligands for trace metal coordination, carves the structural determinants underlying the allosteric nature of the trace metal modulation. The recognition that the identified key residues such as histidines, aspartic and glutamic acids or cysteines in the extracellular domain are different for each P2X receptor subtype and may be different for each metal, highlights the notion that each P2X receptor subtype evolved independent strategies for metal coordination, which form upon the proper three-dimensional folding of the receptor channels. The understanding of the molecular mechanism of allosteric modulation of ligand-operated ionic channels by trace metals is a new contribution to metallo-neurobiology.FONDAPFONDAP1398000113980001virtual::41768-1WOS:000253525900009https://hdl.handle.net/10533/236937enginstname: Conicytreponame: Repositorio Digital RI2.010.1007/s00249-007-0230-7info:eu-repo/grantAgreement/Fondap/13980001https://www.ncbi.nlm.nih.gov/pubmed/17972073Atribución-NoComercial-SinDerivadas 3.0 Chilehttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/info:eu-repo/semantics/openAccessTrace metals in the brain: allosteric modulators of ligand-gated receptor channels, the case of ATP-gated P2X receptorsEur Biophys JArticuloinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttps://hdl.handle.net/10533/236937http://purl.org/coar/resource_type/c_2df8fbb14c0c28ba-308a-47c1-afb7-2607f38e4c08virtual::41768-14c0c28ba-308a-47c1-afb7-2607f38e4c08virtual::41768-110533/236937oai:repositorio.anid.cl:10533/2369372023-07-24 16:51:12.237https://repositorio.anid.clRepositorio ANIDaletelier@anid.cl
dc.title.none.fl_str_mv Trace metals in the brain: allosteric modulators of ligand-gated receptor channels, the case of ATP-gated P2X receptors
dc.title.journal.none.fl_str_mv Eur Biophys J
title Trace metals in the brain: allosteric modulators of ligand-gated receptor channels, the case of ATP-gated P2X receptors
spellingShingle Trace metals in the brain: allosteric modulators of ligand-gated receptor channels, the case of ATP-gated P2X receptors
Huidobro-Toro, J.P.
title_short Trace metals in the brain: allosteric modulators of ligand-gated receptor channels, the case of ATP-gated P2X receptors
title_full Trace metals in the brain: allosteric modulators of ligand-gated receptor channels, the case of ATP-gated P2X receptors
title_fullStr Trace metals in the brain: allosteric modulators of ligand-gated receptor channels, the case of ATP-gated P2X receptors
title_full_unstemmed Trace metals in the brain: allosteric modulators of ligand-gated receptor channels, the case of ATP-gated P2X receptors
title_sort Trace metals in the brain: allosteric modulators of ligand-gated receptor channels, the case of ATP-gated P2X receptors
dc.creator.none.fl_str_mv Huidobro-Toro, J.P.
Lorca, R.A.
Coddou, C.
author Huidobro-Toro, J.P.
author_facet Huidobro-Toro, J.P.
Lorca, R.A.
Coddou, C.
author_role author
author2 Lorca, R.A.
Coddou, C.
author2_role author
author
description Zinc and copper are indispensable trace metals for life with a recognized role as catalysts in enzyme actions. We now review evidence supporting the role of trace metals as novel allosteric modulators of ionotropic receptors: a new and fundamental physiological role for zinc and copper in neuronal and brain excitability. The review is focussed on ionotropic receptor channels including nucleotide receptors, in particular the P2X receptor family. Since zinc and copper are stored within synaptic vesicles in selected brain regions, and released to the synaptic cleft upon electrical nerve ending depolarization, it is plausible that zinc and copper reach concentrations in the synapse that profoundly affect ligand-gated ionic channels, including the ATP-gated currents of P2X receptors. The identification of key P2X receptor amino acids that act as ligands for trace metal coordination, carves the structural determinants underlying the allosteric nature of the trace metal modulation. The recognition that the identified key residues such as histidines, aspartic and glutamic acids or cysteines in the extracellular domain are different for each P2X receptor subtype and may be different for each metal, highlights the notion that each P2X receptor subtype evolved independent strategies for metal coordination, which form upon the proper three-dimensional folding of the receptor channels. The understanding of the molecular mechanism of allosteric modulation of ligand-operated ionic channels by trace metals is a new contribution to metallo-neurobiology.
publishDate 2008
dc.date.issued.none.fl_str_mv 2008
dc.date.accessioned.none.fl_str_mv 2019-12-18T18:14:22Z
2022-07-07T21:58:40Z
dc.date.available.none.fl_str_mv 2019-12-18T18:14:22Z
2022-07-07T21:58:40Z
dc.type.none.fl_str_mv Articulo
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
dc.type.openaire.none.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.folio.none.fl_str_mv 13980001
13980001
dc.identifier.idwos.none.fl_str_mv WOS:000253525900009
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10533/236937
identifier_str_mv 13980001
WOS:000253525900009
url https://hdl.handle.net/10533/236937
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv instname: Conicyt
reponame: Repositorio Digital RI2.0
dc.relation.doi.none.fl_str_mv 10.1007/s00249-007-0230-7
dc.relation.projectid.none.fl_str_mv info:eu-repo/grantAgreement/Fondap/13980001
dc.relation.uri.none.fl_str_mv https://www.ncbi.nlm.nih.gov/pubmed/17972073
dc.rights.none.fl_str_mv Atribución-NoComercial-SinDerivadas 3.0 Chile
http://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rights.driver.none.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv Atribución-NoComercial-SinDerivadas 3.0 Chile
http://creativecommons.org/licenses/by-nc-nd/3.0/cl/
eu_rights_str_mv openAccess
repository.name.fl_str_mv Repositorio ANID
repository.mail.fl_str_mv aletelier@anid.cl
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