期刊
JOURNAL OF NEUROPHYSIOLOGY
卷 113, 期 9, 页码 3356-3374出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/jn.00460.2014
关键词
Na+/K+ pump; seizure; epilepsy; ion concentrations; STDN; intracellular Na+; extracellular K+
资金
- National Institutes of Health [R01 NS059740, R01 NS081243, R01 EB009282, R01 MH099645]
- National Science Foundation Grant [DMS-1009591]
- Russian Foundation for Basic Research Grant [11-01-00001]
- Ministry of Education and Science of the Russian Federation [N 02.B.49.21.0003]
- Lobachevsky State University of Nizhni Novgorod [N 02.B.49.21.0003]
- Russian Science Foundation Grant at Lobachevsky State University of Nizhni Novgorod [14-41-00044]
- Russian Science Foundation [14-41-00044] Funding Source: Russian Science Foundation
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.
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