Anales RANF

S8-02 MODULATION OF P2X7 RECEPTOR ACTIVITY BY EXTRACELLULAR ZN 2+ : IMPLICATIONS FOR MOOD DISORDERS Beata Sperlagh 1 , Gergely Kovacs 1 , Lumei Huang 1, Flóra Gölöncsér 1 1 Institute of Experimental Medicine, Hungarian Academy of Sciences P2X receptors are ligand gated cation channels functioning in homo- or hetero-trimeric assemblies. The channel gating of different P2X receptor subtypes are allosterically modulated by divalent cations and their action is dependent on the individual subtype and the concentration of the cation. Zn 2+ is an essential micronutrient that is concentrated in glutamatergic synaptic vesicles in the hippocampus and has antidepressant-like effect in animal experiments, whilst Zn 2+ deprivation has opposite effect. We and others showed that P2X7R inhibition has also antidepressant effect, therefore we asked how extracellular Zn 2+ modulates P2X7 receptor activity in the hippocampus, and whether the antidepressant effect of Zn 2+ is mediated by inhibition of P2X7Rs. The expression and activity of P2X7Rs was measured in primary mouse hippocampal culture and in acute mouse hippocampal slices, in vivo behavior tests were carried out in wild type and P2X7R deficient (P2rx7-/-) mice. We found that P2X7R immunofluorescence is expressed in both neurons and glia in primary mouse hippocampal culture. P2X7R/pannexin mediated pore formation measured by propidium iodide uptake was dose-dependently inhibited by Zn 2+ . ATP or 3'-O-(4-Benzoyl) benzoyl ATP induced calcium influx in glial cells was also reduced by free zinc ions. Consistently, Zn 2+ inhibited P2X7R mediated glutamate release from hippocampal slices. ZnCl 2 (1 mg/kg i.p.) increased immobility in the forced swim test (FST) and the tail suspension test (TST). P2X7R deficiency also exhibited antidepressant-like effect; however, the effect of ZnCl 2 was only slightly attenuated in P2rx7-/- mice. In conclusion, Zn 2+ has an inhibitory effect on P2X7R function in the hippocampus , whereas its antidepressant-like effect in the TST and FST is largely independent from the overall activity of P2X7Rs.