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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.
AuthorsBárbara P Marquezan, Vinícius R Funck, Clarissa V Oliveira, Letícia M Pereira, Stífani M Araújo, Micheli S Zarzecki, Luiz Fernando F Royes, Ana Flávia Furian, Mauro S Oliveira
JournalEpilepsy research (Epilepsy Res) Vol. 105 Issue 3 Pg. 396-400 (Aug 2013) ISSN: 1872-6844 [Electronic] Netherlands
PMID23602551 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier B.V. All rights reserved.
Chemical References
  • Convulsants
  • Protein Subunits
  • Serine
  • Sodium-Potassium-Exchanging ATPase
  • Pentylenetetrazole
Topics
  • Animals
  • Cerebral Cortex (drug effects, enzymology)
  • Convulsants (toxicity)
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Pentylenetetrazole (toxicity)
  • Phosphorylation (drug effects)
  • Protein Subunits (metabolism)
  • Reaction Time (drug effects)
  • Seizures (chemically induced, pathology)
  • Serine (metabolism)
  • Sodium-Potassium-Exchanging ATPase (metabolism)
  • Time Factors

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