DeLorenzo R J, Pal S, Sombati S
Department of Neurology, Medical College of Virginia of Virginia Commonwealth University, Richmond, VA 23298, USA.
Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14482-7. doi: 10.1073/pnas.95.24.14482.
The molecular basis for developing symptomatic epilepsy (epileptogenesis) remains ill defined. We show here in a well characterized hippocampal culture model of epilepsy that the induction of epileptogenesis is Ca2+-dependent. The concentration of intracellular free Ca2+ ([Ca2+]i) was monitored during the induction of epileptogenesis by prolonged electrographic seizure activity induced through low-Mg2+ treatment by confocal laser-scanning fluorescent microscopy to directly correlate changes in [Ca2+]i with alterations in membrane excitability measured by intracellular recording using whole-cell current-clamp techniques. The induction of long-lasting spontaneous recurrent epileptiform discharges, but not the Mg2+-induced spike discharges, was prevented in low-Ca2+ solutions and was dependent on activation of the N-methyl-D-aspartate (NMDA) receptor. The results provide direct evidence that prolonged activation of the NMDA-Ca2+ transduction pathway causes a long-lasting plasticity change in hippocampal neurons causing increased excitability leading to the occurrence of spontaneous, recurrent epileptiform discharges.
症状性癫痫（癫痫发生）发展的分子基础仍不清楚。我们在此通过一个特征明确的癫痫海马培养模型表明，癫痫发生的诱导是钙离子依赖性的。在通过低镁处理诱导癫痫发生的过程中，利用共聚焦激光扫描荧光显微镜监测细胞内游离钙离子浓度（[Ca2+]i），以通过全细胞电流钳技术进行细胞内记录来测量膜兴奋性的变化，从而将[Ca2+]i的变化与膜兴奋性的改变直接关联起来。在低钙溶液中，长时程自发性反复癫痫样放电的诱导被阻止，但镁离子诱导的尖峰放电未被阻止，且这依赖于N-甲基-D-天冬氨酸（NMDA）受体的激活。这些结果提供了直接证据，即NMDA-钙离子转导途径的长期激活会导致海马神经元发生长期可塑性变化，导致兴奋性增加，进而引发自发性、反复癫痫样放电的发生。
