Pentylenetetrazol-induced seizures are associated with Na⁺,K⁺-ATPase activity decrease and alpha subunit phosphorylation state in the mice cerebral cortex

Epilepsy Res. 2013 Aug;105(3):396-400. doi: 10.1016/j.eplepsyres.2013.03.007. Epub 2013 Apr 17.

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.

Keywords: Convulsion; Epilepsy; Phosphorylation; Sodium pump.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / 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*
  • Seizures / pathology
  • Serine / metabolism
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Time Factors

Substances

  • Convulsants
  • Protein Subunits
  • Serine
  • Sodium-Potassium-Exchanging ATPase
  • Pentylenetetrazole