Decreased calmodulin-NR1 co-assembly as a mechanism for focal epilepsy in cortical dysplasia.
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.
Mikuni
N
N
Department of Neurosciences, The Cleveland Clinic Foundation, OH 44195, USA.
Nishiyama
K
K
Babb
T L
TL
Ying
Z
Z
Najm
I
I
Okamoto
T
T
Lüders
H O
HO
Wylie
C
C
D000293:Adolescent; D002147:Calmodulin / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D002648:Child; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D011233:Precipitin Tests; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D002147:Calmodulin; D016194:Receptors, N-Methyl-D-Aspartate