title: Extracellular ATP differentially affects epileptiform activity via purinergic P2X7 and adenosine A1 receptors in naive and chronic epileptic rats.
abstract: OBJECTIVE
  Adenosine is considered an endogenous anticonvulsant. However, much less is known about the putative effects of its precursor, ATP, on epilepsy. Therefore, we tested whether ATP and its receptors are able to modulate epileptiform activity in the medial entorhinal cortex of the rat.
  
  
  METHODS
  Recurrent epileptiform discharges (REDs) were induced by elevating extracellular potassium concentration combined with application of bicuculline in brain slices from naive and pilocarpine-treated chronic epileptic rats. Field potentials were recorded from layer V/VI of the medial entorhinal cortex.
  
  
  RESULTS
  REDs in slices from naive animals had a higher incidence and a shorter duration than in slices from chronic epileptic animals. Exogenous application of ATP reversibly reduced the incidence of REDs in naive and chronic epileptic slices via activation of adenosine A(1) receptors without discernible P2 receptor effects. This effect was stronger in slices from chronic epileptic rats. In slices from naive rats, the P2X7 receptor antagonist A 740003 slightly but significantly reduced the amplitude of slow field potentials of REDs. In slices from chronic epileptic rats, none of the P2 receptor antagonists affected the parameters of REDs.
  
  
  CONCLUSIONS
  Our results suggest that endogenously released ATP differentially modulates REDs by activation of A(1) and P2X7 receptors. Although it has a minor proepileptic effect by direct activation of P2X7 receptors, its metabolite adenosine reduces the epileptiform activity via activation of A(1) receptors. The exact effect of ATP on neural activity depends on the actual activity of ectonucleotidases and the expression level of the purinergic receptors, which both alter during epileptogenesis. In addition, our data suggest that P2X7 receptor antagonists have a minor antiepileptic effect.
authors.affiliation: Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, Charitplatz 1, Berlin, Germany.
authors.forename: Zin-Juan
authors.initials: ZJ
authors.lastname: Klaft
authors.forename: Steffen B
authors.initials: SB
authors.lastname: Schulz
authors.forename: Anna
authors.initials: A
authors.lastname: Maslarova
authors.forename: Siegrun
authors.initials: S
authors.lastname: Gabriel
authors.forename: Uwe
authors.initials: U
authors.lastname: Heinemann
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Gerevich
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002908:Chronic Disease; D018728:Entorhinal Cortex / Q000187:drug effects / Q000502:physiology*; D004827:Epilepsy / Q000378:metabolism* / Q000503:physiopathology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D058920:Purinergic P2X Receptor Antagonists; D043682:Receptor, Adenosine A1; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate