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

Summary 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 60g/kg, i.p.) was administered to adult male Swiss mice, and Na + ,K + -ATPase activity and phosphorylation state were measured in the cerebral cortex 15min after PTZ administration. Na + ,K + -ATPase activity significantly decreased after PTZ-induced seizures (60mg/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.