Altered transporter-mediated neocortical GABA release in Rasmussen encephalitis.
To learn whether epileptic seizures in Rasmussen encephalitis (RE) may be promoted by insufficient γ-aminobutyric acid (GABA) release. (3) H-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 Ca(2+) concentration ([Ca(2+) ]e ) was inversely related to the amount of release. In RE, the percental decline of additional release upon Cae 2+ 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 [Ca(2+) ]e . Zero [Ca(2+) ]e increased release through the Na(+) /Ca(2+) exchanger additionally elevating intrasynaptosomal Na(+) . This enhanced GABA release probably reflects an antiseizure mechanism. In RE, the additional release gets lost over epilepsy duration.
Section of Clinical Neuropharmacology, Department of Neurosurgery, Albert-Ludwigs University, Freiburg, Germany.
Michael P
MP
Rassner
Vera
V
van Velthoven-Wurster
Georgia
G
Ramantani
Thomas J
TJ
Feuerstein
D004660:Encephalitis / Q000378:metabolism*; D006801:Humans; D019579:Neocortex / Q000187:drug effects / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000819:agonists / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D019831:Sodium-Calcium Exchanger; D005680:gamma-Aminobutyric Acid; D014701:Veratridine