title: Zinc enhances long-term potentiation through P2X receptor modulation in the hippocampal CA1 region.
abstract: Zn²(+) is an essential ion that is stored in and co-released from glutamatergic synapses and it modulates neurotransmitter receptors involved in long-term potentiation (LTP). However, the mechanism(s) underlying Zn²(+) -induced modulation of LTP remain(s) unclear. As the purinergic P2X receptors are relevant targets for Zn²(+) action, we have studied their role in LTP modulation by Zn²(+) in the CA1 region of rat hippocampal slices. Induction of LTP in the presence of Zn²(+) revealed a biphasic effect - 5-50 μm enhanced LTP induction, whereas 100-300 μm Zn²(+) inhibited LTP. The involvement of a purinergic mechanism is supported by the fact that application of the P2X receptor antagonists 2',3'-O-(2,4,6-trinitrophenyl) ATP (TNP-ATP) and periodate-oxidized ATP fully abolished the facilitatory effect of Zn²(+) . Notably, application of the P2X₇ receptor-specific antagonist Brilliant Blue G did not modify the Zn²(+) -dependent facilitation of LTP. Exogenous ATP also produced a biphasic effect - 0.1-1 μm ATP facilitated LTP, whereas 5-10 μm inhibited LTP. The facilitatory effect of ATP was abolished by the application of TNP-ATP and was modified in the presence of 5 μm Zn²(+) , suggesting that P2X receptors are involved in LTP induction and that Zn²(+) leads to an increase in the affinity of P2X receptors for ATP. The latter confirms our previous results from heterologous expression systems. Collectively, our results indicate that Zn²(+) at low concentrations enhances LTP by modulating P2X receptors. Although it is not yet clear which purinergic receptor subtype(s) is responsible for these effects on LTP, the data presented here suggest that P2X₄ but not P2X₇ is involved.
authors.affiliation: Laboratorio de Neurociencias, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, Chile.|Laboratorio de Nucleótidos, Centro de Regulación Celular y Patología, J.V. Luco, Instituto MIFAB, Departamento de Fisiología, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago, Chile.
authors.forename: Ramón A
authors.initials: RA
authors.lastname: Lorca
authors.affiliation: Laboratorio de Neurociencias, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rozas
authors.affiliation: Laboratorio de Neurociencias, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, Chile.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Loyola
authors.affiliation: Laboratorio de Neurociencias, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, Chile.
authors.forename: Sandra
authors.initials: S
authors.lastname: Moreira-Ramos
authors.affiliation: Escuela de Psicología, Universidad de Santiago de Chile, Santiago, Chile.
authors.forename: Marc L
authors.initials: ML
authors.lastname: Zeise
authors.affiliation: Mind/Brain Institute and Department of Neurosciences, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Kirkwood
authors.affiliation: Laboratorio de Nucleótidos, Centro de Regulación Celular y Patología, J.V. Luco, Instituto MIFAB, Departamento de Fisiología, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago, Chile.
authors.forename: J Pablo
authors.initials: JP
authors.lastname: Huidobro-Toro
authors.affiliation: Laboratorio de Neurociencias, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, Chile.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Morales
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000502:physiology*; D004594:Electrophysiology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D058911:Purinergic P2X Receptor Agonists / Q000494:pharmacology; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D058469:Receptors, Purinergic P2X / Q000378:metabolism*; D058848:Receptors, Purinergic P2X4 / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
chemical_list: D058911:Purinergic P2X Receptor Agonists; D058920:Purinergic P2X Receptor Antagonists; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D058469:Receptors, Purinergic P2X; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D015032:Zinc