title: Long-term decrease in Na+,K+-ATPase activity after pilocarpine-induced status epilepticus is associated with nitration of its alpha subunit.
abstract: Temporal lobe epilepsy (TLE) is the most common type of epilepsy with about one third of TLE patients being refractory to antiepileptic drugs. Knowledge about the mechanisms underlying seizure activity is fundamental to the discovery of new drug targets. Brain Na(+),K(+)-ATPase activity contributes to the maintenance of the electrochemical gradients underlying neuronal resting and action potentials as well as the uptake and release of neurotransmitters. In the present study we tested the hypothesis that decreased Na(+),K(+)-ATPase activity is associated with changes in the alpha subunit phosphorylation and/or redox state. Activity of Na(+),K(+)-ATPase decreased in the hippocampus of C57BL/6 mice 60 days after pilocarpine-induced status epilepticus (SE). In addition, the Michaelis-Menten constant for ATP of α2/3 isoforms increased at the same time point. Nitration of the α subunit may underlie decreased Na(+),K(+)-ATPase activity, however no changes in expression or phosphorylation state at Ser(943) were found. Further studies are necessary define the potential of nitrated Na(+),K(+)-ATPase as a new therapeutic target for seizure disorders.
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil.
authors.forename: Vinícius Rafael
authors.initials: VR
authors.lastname: Funck
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil.
authors.forename: Leandro Rodrigo
authors.initials: LR
authors.lastname: Ribeiro
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil.
authors.forename: Letícia Meier
authors.initials: LM
authors.lastname: Pereira
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil.
authors.forename: Clarissa Vasconcelos
authors.initials: CV
authors.lastname: de Oliveira
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil.
authors.forename: Jéssica
authors.initials: J
authors.lastname: Grigoletto
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil; Graduate Program in Biological Sciences: Biochemistry, Federal University of Santa Maria, Santa Maria, Brazil.
authors.forename: Michele Rechia
authors.initials: MR
authors.lastname: Fighera
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil; Graduate Program in Biological Sciences: Biochemistry, Federal University of Santa Maria, Santa Maria, Brazil.
authors.forename: Luiz Fernando Freire
authors.initials: LF
authors.lastname: Royes
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil.
authors.forename: Ana Flávia
authors.initials: AF
authors.lastname: Furian
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil; Graduate Program in Biological Sciences: Biochemistry, Federal University of Santa Maria, Santa Maria, Brazil. Electronic address: ms.oliveira@ufsm.br.
authors.forename: Mauro Schneider
authors.initials: MS
authors.lastname: Oliveira
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D006624:Hippocampus / Q000201:enzymology*; D007527:Isoenzymes; D008297:Male; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D010766:Phosphorylation; D010862:Pilocarpine; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D013226:Status Epilepticus / Q000201:enzymology*
chemical_list: D007527:Isoenzymes; D010862:Pilocarpine; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Epilepsy; Nitrotyrosine; Pilocarpine; Sodium pump