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

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.