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 fo r 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 r ecordings from three patients (aged 6, 14 and 18 years) with focal epilepsy associated with cortical dysplasia. In all patients, the co-assembly of ca lmodulin and NMDAR1 was decreased in epileptogenic dysplastic cortex compar ed with normal appearing non-epileptogenic cortex, while there was no signi ficant difference in the total protein levels of calmodulin or NMDAR1 betwe en the two EEG groups. These results suggest that decreased calmodulin-NMDA R1 co-assembly is a cellular mechanism that contributes to hyperexcitabilit y in dysplastic cortical neurons and in focal seizure onsets. NeuroReport 1 0:1609-1612 (C) 1999 Lippincott Williams & Wilkins.