Ionic dynamics mediate spontaneous termination of seizures and postictal depression state

Maxim Bazhenov (February 6, 2013)

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Abstract

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.