Altered transporter-mediated neocortical GABA release in Rasmussen encephalitis


Address correspondence to Thomas J. Feuerstein, Section of Clinical Neuropharmacology, Department of Neurosurgery, Albert-Ludwigs University, Breisacher Strasse 64, D-79106 Freiburg, Germany. E-mail:


To learn whether epileptic seizures in Rasmussen encephalitis (RE) may be promoted by insufficient γ-aminobutyric acid (GABA) release. 3H-GABA was released from neocortical synaptosomes through transporter reversal following intrasynaptosomal Na+ accumulation by veratridine that prevents inactivation of Na+ channels. Tissues of three RE patients were compared with those of nine non-RE. In RE, the release was markedly reduced. In non-RE, the extracellular Ca2+ concentration ([Ca2+]e) was inversely related to the amount of release. In RE, the percental decline of additional release upon inline image withdrawal was linked with the presurgical duration of epilepsy. Permanent opening of Na+ channels by veratridine resembles maximal frequency of action potentials corresponding to epileptic seizures. These are preceded by a fall in [Ca2+]e. Zero [Ca2+]e increased release through the Na+/Ca2+ exchanger additionally elevating intrasynaptosomal Na+. This enhanced GABA release probably reflects an antiseizure mechanism. In RE, the additional release gets lost over epilepsy duration.