NON-SYNAPTIC MECHANISMS | Modulation of Neuronal Excitability by Changes in Extracellular Ion Composition

Abstract

Measurements with ion selective electrodes, and more recently with fluorescent ion indicators, in different species (from mice to man) have revealed that seizures and seizure-like events are accompanied by strong transmembrane ion fluxes leading to alterations of intra- and extracellular ion concentrations and to water movements and cell swelling. Irrespective of the mode of seizure induction, experiments have shown that convulsant seizures are associated with rises in potassium concentration, biphasic changes in extracellular sodium, and chloride concentration, as well as pH changes and decreases in extracellular calcium concentration. During seizure activity, transmembrane ion fluxes and anaerobic metabolism lead to water flux into cellular elements and shrinkage of the extracellular space (ES). Rises in extracellular potassium concentration, decreases in extracellular calcium concentration, reductions of ES size, and intracellular chloride accumulation can support seizure development. In contrast, accumulation of sodium ions inside neurons will help to terminate seizures by activation of the electrogenic Na-K-ATPase.