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Zinc enhances long‐term potentiation through P2X receptor modulation in the hippocampal CA1 region
Author(s) -
Lorca Ramón A.,
Rozas Carlos,
Loyola Sebastian,
MoreiraRamos Sandra,
Zeise Marc L.,
Kirkwood Alfredo,
HuidobroToro J. Pablo,
Morales Bernardo
Publication year - 2011
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2010.07589.x
Subject(s) - long term potentiation , purinergic receptor , receptor , chemistry , hippocampal formation , microbiology and biotechnology , neuroscience , biology , biophysics , biochemistry
Zn 2+ 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 Zn 2+ ‐induced modulation of LTP remain(s) unclear. As the purinergic P2X receptors are relevant targets for Zn 2+ action, we have studied their role in LTP modulation by Zn 2+ in the CA1 region of rat hippocampal slices. Induction of LTP in the presence of Zn 2+ revealed a biphasic effect – 5–50 μ m enhanced LTP induction, whereas 100–300 μ m Zn 2+ 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 Zn 2+ . Notably, application of the P2X 7 receptor‐specific antagonist Brilliant Blue G did not modify the Zn 2+ ‐dependent facilitation of LTP. Exogenous ATP also produced a biphasic effect – 0.1–1 μ m ATP facilitated LTP, whereas 5–10 μ m inhibited LTP. The facilitatory effect of ATP was abolished by the application of TNP‐ATP and was modified in the presence of 5 μ m Zn 2+ , suggesting that P2X receptors are involved in LTP induction and that Zn 2+ 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 Zn 2+ 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 P2X 4 but not P2X 7 is involved.