title: 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.
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, California;
authors.forename: Giri P
authors.initials: GP
authors.lastname: Krishnan
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, California;
authors.forename: Gregory
authors.initials: G
authors.lastname: Filatov
authors.affiliation: Neuroscience Institute and Department of Mathematics and Statistics, Georgia State University, Atlanta, Georgia; and Institute for Information Technology, Mathematics and Mechanics, Lobachevsky State University of Nizhni Novgorod, Nizhni Novgorod, Russia.
authors.forename: Andrey
authors.initials: A
authors.lastname: Shilnikov
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, California; maksim.bazhenov@ucr.edu.
authors.forename: Maxim
authors.initials: M
authors.lastname: Bazhenov
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000503:physiopathology*; D003198:Computer Simulation; D004558:Electric Stimulation; D004827:Epilepsy / Q000473:pathology; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism* / Q000502:physiology*; D017711:Nonlinear Dynamics; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase; D013569:Synapses / Q000502:physiology
chemical_list: D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium
keywords: Na+/K+ pump; STDN; epilepsy; extracellular K+; intracellular Na+; ion concentrations; seizure