Ionic dynamics mediate spontaneous termination of seizures and postictal depression state

Maxim Bazhenov (February 6, 2013)

Please install the Flash Plugin


Ionic concentrations fluctuate significantly during seizures. Substantial increase of extracellular K+ is found during electrically- or pharmacologically-induced paroxysmal activity, along with increase of intracellular Na+. These changes of the ionic concentrations trigger various homeostasis mechanisms such as glial uptake and Na+/K+ ATPase. While Na+/K+ ATPase is one of the most studied proteins, its role in epilepsy remains unclear. Using computational model of in vivo epileptiform activity, we found that increase of intracellular Na+ during epileptiforms leads to significant activation of Na+/K+ ATPase; this increase mediates hyperpolarizing current by Na+/K+ pump that contributes to termination of seizure and postictal depression state. Deficiencies of the Na+/K+ ATPase promote continuous epileptiform activity. In terms of dynamics, the mechanism underlying the smooth transition is due to a safe bifurcation of a homoclinic orbit of a saddle-node equilibrium state terminating the quiescence period of bursting. Overall, our study demonstrated a complex role played by Na+/K+ ATPase in developing of epileptiform activity and may suggest new targets for antiepileptic drugs.