Excitatory amino acids and epilepsy-induced changes in extracellular space size

Convulsant and stimulus induced seizures are associated with Ca, Na, K and Cl concentration changes in the extracellular space (ES), which are a resultant of transmembrane ionic fluxes and of changes in the ES size. The ES decreases on average by 30% during a single seizure. An analysis of the causes of ES size changes reveal a large contribution from the spatial glia K buffer mechanism which may account for up to 60% of the ES decreases. NaCl and KCl uptake into cells as well as increases in intracellular osmolarity due to anaerobic glycolysis contribute less to the local cytotoxic edema but account for a net gain of osmotic active particle at the site of the focus. Excitatory amino acids such as glutamate, aspartate, N-methyl-D-aspartate (NMDA), kainate and quisqualate also lead to Na, Cl and eventually Ca uptake into cells and to release of K with dose dependent decreases in [Na]o, [Ca]o and [Cl]o, increases in [K]o and transient decreases in ES size by up to 80% which are possibly associated with a net reduction of osmotically active particles. The predominant cause for this cytotoxic edema is NaCl uptake into cells but spatial K buffering through glial cells also contributes to this type of edema. The possible consequences of the various ion movements and the changes in osmolarity as well as ES size for tissue vulnerability are discussed.