Adenosine A1 receptor negatively modulates Gabaa receptor mediated postsynaptic currents in rat hippocampal CA1 pyramidal cells

Abstract

Event Abstract Back to Event Adenosine A1 receptor negatively modulates Gabaa receptor mediated postsynaptic currents in rat hippocampal CA1 pyramidal cells Diogo Rombo1*, Raquel Alice-Dias1, Joaquim Alexandre-Ribeiro1 and Ana Maria-Sebastiao1 1 University of Lisbon, Institute of Pharmacology and Neurosciences, Institute of Molecular Medicine, Faculty of Medicine, Portugal Adenosine acts in the hippocampus as a modulator of neuronal excitability either by directly modulating the glutamatergic excitatory circuit or by modification of GABA inhibition. Previous studies have focused on this modulatory role of adenosine both in glutamatergic communication and in presynaptic GABA function. However, much less is known about any possible role of adenosine on postsynaptic GABA modulation. With this work we intended to investigate the role of adenosine – via inhibitory A1 and facilitatory A2A receptors – on the modulation of postsynaptic currents mediated by ionotropic GABAA-type receptors. Whole-cell recordings in voltage-clamp mode (Vh=-70mV) were used in hippocampal slices of young (3-5 weeks) male Wistar rats. Individual slices were fixed in a recording chamber and continuously superfused with artificial cerebrospinal fluid containing (in mM): NaCl 124; KCl 3; NaH2PO4 1.25; NaHCO3 26; MgSO4 1; CaCl2 2 and glucose 10, pH 7.4, gassed with 95% O2 and 5% CO2. The internal solution consisted of (in mM): K-gluconate 125; KCl 11; CaCl2 0.1; MgCl2 2; EGTA 1; HEPES 10; MgATP 2 ; NaGTP 0.3 and phosphocreatine 10, pH 7.3, adjusted with KOH (1M). GABAA-mediated currents were evoked through a micropipette containing muscimol (30μM), a GABAA receptor agonist, coupled to a pressure ejection system. Single pulses of 10ms and 6psi were applied every 2min. Experiments were rejected when the holding potential or the series resistance varied by more than 20%.Bath application of CGS21680 (30nM), an adenosine A2A receptor agonist, induced no statistically significant differences on muscimol evoked currents (101±2.1% of baseline, n=5, p=0.747). The superfusion of the adenosine A1 receptor agonist, CPA (10nM), significantly decreased the peak amplitude of GABAergic responses in 12 of 17 cells tested with a maximum effect (46±3.9%, n=12, p<0.0001) reached within less than 45min. This effect of CPA was not reversible within 40min after washing it out from the bath. However, the application of DPCPX (50nM), an adenosine A1 receptor antagonist, induced the recovery of the muscimol evoked currents towards 80% of the pre-control value (n=1). This effect of CPA was concentration dependent since the application of 30nM of CPA caused a greater inhibition than 10nM of CPA (n=2). Together, these results suggest that postsynaptic GABAA receptor mediated currents are modulated by adenosine A1 receptor, but not A2A receptor, in rat hippocampal CA1 pyramidal cells. Conference: 11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009. Presentation Type: Poster Presentation Topic: Neuronal Communication Citation: Rombo D, Alice-Dias R, Alexandre-Ribeiro J and Maria-Sebastiao A (2009). Adenosine A1 receptor negatively modulates Gabaa receptor mediated postsynaptic currents in rat hippocampal CA1 pyramidal cells. Front. Neurosci. Conference Abstract: 11th Meeting of the Portuguese Society for Neuroscience. doi: 10.3389/conf.neuro.01.2009.11.115 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Aug 2009; Published Online: 11 Aug 2009. * Correspondence: Diogo Rombo, University of Lisbon, Institute of Pharmacology and Neurosciences, Institute of Molecular Medicine, Faculty of Medicine, Lisbon, Portugal, d.rombo@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Diogo Rombo Raquel Alice-Dias Joaquim Alexandre-Ribeiro Ana Maria-Sebastiao Google Diogo Rombo Raquel Alice-Dias Joaquim Alexandre-Ribeiro Ana Maria-Sebastiao Google Scholar Diogo Rombo Raquel Alice-Dias Joaquim Alexandre-Ribeiro Ana Maria-Sebastiao PubMed Diogo Rombo Raquel Alice-Dias Joaquim Alexandre-Ribeiro Ana Maria-Sebastiao Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.