Glutamate and gamma-aminobutyric acid content and release of synaptosomes from temporal lobe epilepsy patients

During surgical intervention in medically refractory temporal lobe epilepsy (TLE) patients, diagnosed with either mesial temporal robe sclerosis (MTS) - or tumor (T)-associated TLE, biopsies were taken from the anterior tempor al neocortex and the hippocampal region. Synaptosomes, isolated from these biopsies were used to study intrasynaptosomal Ca2+ levels ([Ca2+](i)), and glutamate and gamma-aminobutyric acid (GABA) contents and release. All syna ptosomal preparations demonstrated a basal [Ca2+](i) of about 200 nM, excep t neocortical synaptosomes from MTS-associated TLE patients (420 nM). K+-in duced depolarization resulted in a robust increase of the basal [Ca2+](i) i n all preparations. Neocortical synaptosomes from TLE patients contained 22 .9 +/- 3.0 nmol glutamate and 4.6 +/- 0.5 nmol GABA per milligram synaptoso mal protein, whereas rat cortical synaptosomes contained twice as much glut amate and four times as much GABA. Hippocampal synaptosomes from MTS-associ ated TLE patients, unlike those from T-associated TLE patients, contained a bout 70% less glutamate and 55% less GABA than neocortical synaptosomes. Ex pressed as percentage of total synaptosomal content, synaptosomes from MTS- associated TLE patients exhibited an increased basal and a reduced K+-induc ed glutamate and GABA release compared to rat cortical synaptosomes. In MTS -associated TLE patients, only GABA release from neocortical synaptosomes w as partially Ca2+-dependent. Control experiments in rat synaptosomes demons trated that at least part of the reduction in K+-induced release can be asc ribed to resection-induced hypoxia in biopsies. Thus, synaptosomes from MTS -associated TLE patients exhibit a significant K+-induced increase in [Ca2](i), but the consequent release of glutamate and GABA is severely impaired . Our data show that at least part of the differences in glutamate and GABA content and release between human biopsy material and fresh rat tissue is due to the resection time. (C) 2000 Wiley-Liss, Inc.