Electrogenic properties of the Na+/K+ATPase control transitions between normal and pathological brain states

Abstract

Ionic concentrations fluctuate significantly during epileptic seizures. In this study, using a combination of in vitro electrophysiology, computer modeling, and dynamical systems analysis, we demonstrate that changes in the potassium and sodium intra- and extracellular ion concentrations ([K+] and [Na+], respectively) during seizure affect the neuron dynamics by modulating the outward Na+/K+pump current. First, we show that an increase of the outward Na+/K+pump current mediates termination of seizures when there is a progressive increase in the intracellular [Na+]. Second, we show that the Na+/K+pump current is crucial in maintaining the stability of the physiological network state; a reduction of this current leads to the onset of seizures via a positive-feedback loop. We then present a novel dynamical mechanism for bursting in neurons with a reduced Na+/K+pump. Overall, our study demonstrates the profound role of the current mediated by Na+/K+ATPase on the stability of neuronal dynamics that was previously unknown.