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

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.