Decreased calmodulin-NR1 co-assembly as a mechanism for focal epilepsy in cortical dysplasia

被引:14
作者
Mikuni, N
Nishiyama, K
Babb, TL
Ying, Z
Najm, I
Okamoto, T
Lüders, HO
Wylie, C
机构
[1] Cleveland Clin Fdn, Dept Neurosci NC3104, Cleveland, OH 44195 USA
[2] Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA
关键词
calmodulin; co-precipitation; cortical dysplasia; epilepsy; NMDAR1;
D O I
10.1097/00001756-199905140-00040
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
THE NMDA receptor is one of the ionotropic glutamate receptors essential for excitatory neurotransmission. The NMDAR1 subunit is inactivated by direct interaction with calmodulin. The protein levels of calmodulin, NMDAR1 and their complex were quantified in tissue resected from epileptogenic and non-epileptogenic cortical areas as determined by chronic subdural electrode recordings from three patients (aged 6, 14 and 18 years) with focal epilepsy associated with cortical dysplasia. In all patients, the co-assembly of calmodulin and NMDAR1 was decreased in epileptogenic dysplastic cortex compared with normal appearing non-epileptogenic cortex, while there was no significant difference in the total protein levels of calmodulin or NMDAR1 between the two EEG groups. These results suggest that decreased calmodulin-NMDAR1 co-assembly is a cellular mechanism that contributes to hyperexcitability in dysplastic cortical neurons and in focal seizure onsets. NeuroReport 10:1609-1612 (C) 1999 Lippincott Williams & Wilkins.
引用
收藏
页码:1609 / 1612
页数:4
相关论文
共 18 条
[1]  
BABB TL, 1989, J NEUROSCI, V9, P2562
[2]   Inactivation of NMDA receptors by direct interaction of calmodulin with the NR1 subunit [J].
Ehlers, MD ;
Zhang, S ;
Bernhardt, JP ;
Huganir, RL .
CELL, 1996, 84 (05) :745-755
[3]   SURGICAL-TREATMENT OF EPILEPSY DUE TO CORTICAL DYSPLASIA - CLINICAL AND EEG FINDINGS [J].
HIRABAYASHI, S ;
BINNIE, CD ;
JANOTA, I ;
POLKEY, CE .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1993, 56 (07) :765-770
[4]   SURGICAL PATHOLOGY OF EPILEPSY - A REVIEW [J].
JAY, V ;
BECKER, LE .
PEDIATRIC PATHOLOGY, 1994, 14 (04) :731-750
[5]  
Krupp JJ, 1996, MOL PHARMACOL, V50, P1680
[6]   Ca2+-dependent inactivation of NMDA receptors: Fast kinetics and high Ca2+ sensitivity in rat dorsal horn neurons [J].
Kyrozis, A ;
Albuquerque, C ;
Gu, JG ;
MacDermott, AB .
JOURNAL OF PHYSIOLOGY-LONDON, 1996, 495 (02) :449-463
[7]  
LEGENDRE P, 1993, J NEUROSCI, V13, P674
[8]   NMDA-RECEPTOR ACTIVATION INCREASES CYTOPLASMIC CALCIUM-CONCENTRATION IN CULTURED SPINAL-CORD NEURONS [J].
MACDERMOTT, AB ;
MAYER, ML ;
WESTBROOK, GL ;
SMITH, SJ ;
BARKER, JL .
NATURE, 1986, 321 (6069) :519-522
[9]   THE ACTION OF N-METHYL-D-ASPARTIC ACID ON MOUSE SPINAL NEURONS IN CULTURE [J].
MAYER, ML ;
WESTBROOK, GL .
JOURNAL OF PHYSIOLOGY-LONDON, 1985, 361 (APR) :65-90
[10]   Calcium-induced inactivation of NMDA receptor-channels evolves independently of run-down in cultured rat brain neurones [J].
Medina, I ;
Filippova, N ;
Bakhramov, A ;
Bregestovski, P .
JOURNAL OF PHYSIOLOGY-LONDON, 1996, 495 (02) :411-427