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-asparate (NMDA) receptors, but not 2-amino-5-phosphonovaleric acid (AP-5; an antagonist of NMDA receptors). Domoic acid given at 5 microM also elevated [Ca2+]i levels in a second population (36%) of neurons in which the effect was only partially inhibited by 100 microM CNQX. Nimodipine given at 300 nM prevented the elevation in [Ca2+]i caused by 50 nM and 5 microM 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.