title: Pentylenetetrazol-induced seizures are associated with Na⁺,K⁺-ATPase activity decrease and alpha subunit phosphorylation state in the mice cerebral cortex.
abstract: The present study aimed to investigate whether Na(+),K(+)-ATPase activity and phosphorylation state of the catalytic α subunit are altered by pentylenetetrazol (PTZ)-induced seizures. PTZ (30, 45 or 60 g/kg, i.p.) was administered to adult male Swiss mice, and Na(+),K(+)-ATPase activity and phosphorylation state were measured in the cerebral cortex 15 min after PTZ administration. Na(+),K(+)-ATPase activity significantly decreased after PTZ-induced seizures (60 mg/kg). Immunoreactivity of phosphorylated Ser943 at α subunit was increased after PTZ-induced seizures. A significant positive correlation between Na(+),K(+)-ATPase activity and latency to myoclonic jerks and generalized seizures was found. Conversely, a strong negative correlation between Ser943 phosphorylation and latency to generalized seizures was detected. Given the role of Na(+),K(+)-ATPase as a major regulator of brain excitability, Ser943 at Na(+),K(+)-ATPase α subunit may represent a potentially valuable new target for drug development for seizure disorders.
authors.affiliation: Federal University of Santa Maria, Pharmacology Graduate Program, Department of Physiology and Pharmacology, Santa Maria 97105-900, Brazil.
authors.forename: Bárbara P
authors.initials: BP
authors.lastname: Marquezan
authors.forename: Vinícius R
authors.initials: VR
authors.lastname: Funck
authors.forename: Clarissa V
authors.initials: CV
authors.lastname: Oliveira
authors.forename: Letícia M
authors.initials: LM
authors.lastname: Pereira
authors.forename: Stífani M
authors.initials: SM
authors.lastname: Araújo
authors.forename: Micheli S
authors.initials: MS
authors.lastname: Zarzecki
authors.forename: Luiz Fernando F
authors.initials: LF
authors.lastname: Royes
authors.forename: Ana Flávia
authors.initials: AF
authors.lastname: Furian
authors.forename: Mauro S
authors.initials: MS
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology*; D003292:Convulsants / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D021122:Protein Subunits / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced* / Q000473:pathology; D012694:Serine / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013997:Time Factors
chemical_list: D003292:Convulsants; D021122:Protein Subunits; D012694:Serine; D000254:Sodium-Potassium-Exchanging ATPase; D010433:Pentylenetetrazole
keywords: Convulsion; Epilepsy; Phosphorylation; Sodium pump