Neuronal hyperactivity has been shown to cause transient changes in ionic concentrations as well as in the volume of the extracellular space (ECS). During enhanced neuronal activity in the sensorimotor cortex of the cat, increases in the extracellular K+ concentration to a ceiling value of 10 mM have been observed concomitant with decreases in the Na+ concentration of similar magnitude. Simultaneously, the Cl- concentration rose steadily during the enhanced neuronal activity, and the extracellular space decreased by about 30%. A mathematical model allowed the interpretation of these concentration and volume changes as results of K+ release by active neurons in exchange for Na+, removal of K+ from the ECS by spatial glial buffering and movements of KCl into glial cells, as well as cell swelling due to metabolically induced transient increases in cellular osmolarity. Similar mechanisms have also been found to operate in gliotic scar tissue, where glial cells appeared to function the same way as in normal cortex, in rat hippocampal slices, and in preparations studied by other investigators.