Glutamate receptors and calcium entry mechanisms for domoic acid in hippocampal neurons

DOMOIC acid (50 nM) elevates cytosolic free calcium ([Ca2+](i)) levels in 49% of the hippocampal pyramidal neurons isolated from postnatal day one (PND1) rats. This effect was prevented by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; an antagonist of non-N-methyl-D-aspartate (NMDA) receptors, but not 2-amino-5-phosphonovaleric acid (AP-5; an antagonist of NMDA receptors). Domoic acid given at 5 mu M also elevated [Ca2+](i) levels in a second population (36%) of neurons in which the effect was only partially inhibited by 100 mu M CNQX. Nimodipine given at 300 nM prevented the elevation in [Ca2+](i) caused by 50 nM and 5 mu M domoic acid, indicating that domoic acid induced Ca2+ entry through type L voltage dependent calcium channels. These results provide evidence for at least two domoic acid-sensitive non-NMDA receptor subtypes in primary cultures of neonatal hippocampal pyramidal cells and indicate that voltage-dependent calcium channels are a primary calcium entry mechanism for domoic acid action.