Glutamate Receptor, Ionotropic, N-Methyl-D-Aspartate Associated Protein 1 (GRINA)

Synaptic and extrasynaptic NMDA receptors have opposite effects on CREB function, gene regulation, and neuronal survival. Calcium entry through synaptic NMDA receptors induced CREB activity and brain-derived neurotrophic factor (BDNF) gene expression as strongly as did stimulation of L-type calcium channels. In contrast, calcium entry through extrasynaptic NMDA receptors, triggered by bath glutamate exposure or hypoxic/ischemic conditions, activated a general and dominant CREB shut-off pathway that blocked induction of BDNF expression. GRINA is outside the critical region for BFNC. However, another form of epilepsy, idiopathic generalized epilepsy has been mapped to distal 8q24; the GRINA locus may be a candidate for this epileptic disorder.