Changes in Extracellular Ions Associated with Epileptiform Discharges

Abstract

Although it has been widely hypothesized that in the central nervous system of mammals the chemical composition of the extracellular fluid is maintained constant through precise regulatory mechanisms, it has become increasingly clear in the last 20 years that significant changes may occur during intense neuronal activity. In this respect, the development of ion-selective microelectrodes (Ammann, 1986) has been a decisive factor to determine the precise nature and extent of the possible ionic changes in the extracellular space. Indeed, it has long been known that nerve cell function is essentially underlain by transmembrane ionic currents, inwardly or outwardly directed, induced either through changes in membrane potential or the action of neurotransmitters. Therefore, any sustained activity of nerve cell could, in principle, alter the ion content of the extracellular or intracellular compartments. Thus, it has been shown that intense neuronal activity is associated with changes in the concentration of extracellular potassium ([K+]o), sodium ([Na+]o), calcium ([Ca2+]o), magnesium ([Mg2+]o), and chloride ([Cl−]o) ions and in pH (Benninger et al., 1980; ten Bruggencate et al., 1976; Dietzel et al., 1982; Futamachi et al., 1974; Heinemann and Lux, 1975; Kraig and Nicholson, 1978; Lux and Neher, 1973; Morris and Krnjevic, 1973; Nicholson et al., 1978; Prince et al., 1973; Pumain and Heinemann, 1985; Somjen, 1979, 1980; Sykova et al., 1976; Urbanics et al., 1978). The magnitude of the ion changes in the extracellular space depends not only on the transmembrane ionic fluxes but also on the volume of distribution of these ions and on how they migrate in the extracellular space.