André Véronique M, Flores-Hernández Jorge, Cepeda Carlos, Starling Amaal J, Nguyen Snow, Lobo Mary Kay, Vinters Harry V, Levine Michael S, Mathern Gary W
Mental Retardation Research Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Cereb Cortex. 2004 Jun;14(6):634-46. doi: 10.1093/cercor/bhh024. Epub 2004 Mar 28.
The subunit composition of glutamate receptors affects their functional properties, and could contribute to abnormal electrophysiology in pediatric cortical dysplasia (CD). We examined electrophysiological responses and subunit assembly of N-methyl-D-aspartate (NMDA) receptors in acutely dissociated normal-appearing pyramidal and cytomegalic neurons from CD tissue and normal-appearing pyramidal neurons from non-CD tissue. In most cytomegalic and approximately 30% of normal-appearing pyramidal neurons from CD tissue, NMDA currents showed decreased Mg(2+) sensitivity compared with neurons from non-CD tissue. Ifenprodil had less effect in CD compared with non-CD neurons, indicating a functional loss of NR2B subunits. NMDA-evoked current density was decreased in cytomegalic compared with normal-appearing neurons. Single-cell reverse transcriptase polymerase chain reaction showed that all non-CD neurons expressed NR2B subunit mRNA. By comparison, 22% of pyramidal neurons in CD tissue lacked NR2B mRNA. Immunofluorescence showed a decrease in NR2B subunit expression in cytomegalic neurons and a subset of normal-appearing pyramidal neurons from CD tissue. Taken together, these results demonstrate the presence of NMDA receptors with altered subunit composition and Mg(2+) sensitivity that could contribute to functional abnormalities in CD.
谷氨酸受体的亚基组成会影响其功能特性，可能导致小儿皮质发育异常（CD）中的异常电生理现象。我们检测了急性分离的来自CD组织的外观正常的锥体神经元和巨细胞神经元以及来自非CD组织的外观正常的锥体神经元中N-甲基-D-天冬氨酸（NMDA）受体的电生理反应和亚基组装情况。在大多数巨细胞神经元以及约30%来自CD组织的外观正常的锥体神经元中，与来自非CD组织的神经元相比，NMDA电流显示出Mg(2+)敏感性降低。与非CD神经元相比，艾芬地尔在CD神经元中的作用较小，表明NR2B亚基功能丧失。与外观正常的神经元相比，巨细胞神经元中NMDA诱发的电流密度降低。单细胞逆转录酶聚合酶链反应显示，所有非CD神经元均表达NR2B亚基mRNA。相比之下，CD组织中22%的锥体神经元缺乏NR2B mRNA。免疫荧光显示，巨细胞神经元以及CD组织中一部分外观正常的锥体神经元中NR2B亚基表达减少。综上所述，这些结果表明存在亚基组成和Mg(2+)敏感性改变的NMDA受体，这可能导致CD中的功能异常。
