title: ATP contributes to the generation of network-driven giant depolarizing potentials in the neonatal rat hippocampus.
abstract: In the immature hippocampus, the so-called 'giant depolarizing potentials' (GDPs) are network-driven synaptic events generated by the synergistic action of glutamate and GABA. Here we tested the hypothesis that ATP, a widely distributed neurotransmitter, directly contributes to the network activity during the first postnatal week. We found that in CA3 pyramidal cells, in the presence of the adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), ATP produced a transient facilitation of GDPs followed by a depressant effect. A similar biphasic effect was produced by blockade of the ectoATPase activity with 6-N,N-diethyl-D-beta,gamma-dibromomethylene ATP (ARL-67156). The effects of exogenous and endogenous ATP on GDPs were prevented by the P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS). On pyramidal cells, ATP upregulated spontaneous action-potential-dependent GABA(A)-mediated synaptic events (GABA-SPSPs), suggesting a network-driven effect. Recordings from interneurones allowed comparison of ATP effects on GABAergic and glutamatergic synaptic activity. While ATP depressed GABA-SPSPs via metabotropic P2Y(1) receptors, it up- and downregulated glutamatergic SPSPs via PPADS-sensitive receptors. Thus, ATP exerts an excitatory action on CA3 pyramidal cells via facilitation of GDPs and SPSPs. This excitatory drive is propagated to pyramidal cells by interneurons that represent the 'common pathway' for generation of GDPs and SPSPs. Our results show that ATP operating via distinct P2X and P2Y receptors directly contributes to modulate network activity at the early stages of postnatal development.
authors.affiliation: Neuroscience Programme, International School for Advanced Studies, Via Beirut 2-4, 34014 Trieste, Italy.
authors.forename: Victoria F
authors.initials: VF
authors.lastname: Safiulina
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Kasyanov
authors.forename: Elena
authors.initials: E
authors.lastname: Sokolova
authors.forename: Enrico
authors.initials: E
authors.lastname: Cherubini
authors.forename: Rashid
authors.initials: R
authors.lastname: Giniatullin
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000502:physiology; D058472:Receptors, Purinergic P2Y1; D014970:Xanthines / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: C546384:P2ry1 protein, rat; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D014970:Xanthines; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine