title: Stabilizing effects of extracellular ATP on synaptic efficacy and plasticity in hippocampal pyramidal neurons.
abstract: The role of adenosine triphosphate (ATP) as a neurotransmitter and extracellular diffusible messenger has recently received considerable attention because of its possible participation in the regulation of synaptic plasticity. However, the possible contribution of extracellular ATP in maintaining and regulating synaptic efficacy during intracellular ATP depletion is understudied. We tested the effects of extracellular ATP on excitatory postsynaptic currents (EPSCs) evoked in CA1 pyramidal neurons by Schaffer collateral stimulation. In the absence of intracellular ATP, EPSC rundown was neutralized when a low concentration of ATP (1 microm) was added to the extracellular solution. Adenosine and ATP analogues did not prevent the EPSC rundown. The P(2) antagonists piridoxal-5'-phosphate-azophenyl 2',4'-disulphonate (PPADS) and reactive blue-2, and the P(1) adenosine receptor antagonist 8-cyclopentyltheophylline (CPT) had no detectable effects in cells depleted of ATP. However, the protective action of extracellular ATP on synaptic efficacy was blocked by extracellular application of the protein kinase inhibitors K252b and staurosporine. In contrast, K252b and staurosporine per se did not interfere with synaptic transmission in ATP loaded cells. Without intracellular ATP, bath-applied caffeine induced a transient (< 35 min) EPSC potentiation that was transformed into a persistent long-term potentiation (> 80 min) when 1 microm ATP was added extracellularly. An increased probability of transmitter release paralleled the long-term potentiation induced by caffeine, suggesting that it originated presynaptically. Therefore, we conclude that extracellular ATP may operate to maintain and regulate synaptic efficacy and plasticity in conditions of abnormal intracellular ATP depletion by phosphorylation of a surface protein substrate via activation of ecto-protein kinases.
authors.affiliation: Instituto Cajal, CSIC, Avenida Doctor Arce 37, 28002-Madrid, Spain. eduardo.martin@uclm.es
authors.forename: Eduardo D
authors.initials: ED
authors.lastname: Martín
authors.forename: Washington
authors.initials: W
authors.lastname: Buño
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002110:Caffeine / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005110:Extracellular Space; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D058919:Purinergic P2 Receptor Antagonists; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D058919:Purinergic P2 Receptor Antagonists; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C022571:adenosine 5'-O-(3-thiotriphosphate); C053907:8-cyclopentyl-1,3-dimethylxanthine; D002110:Caffeine; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D013806:Theophylline