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.
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Marine Biotoxins Program, U.S. National Marine Fisheries Services, Charleston, SC, USA.
Ramsdell
J S
JS
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D009553:Nimodipine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; C012301:domoic acid; D007608:Kainic Acid; D002118:Calcium