Two distinct quisqualate receptors regulate Ca²⁺ homeostasis in hippocampal neurons in vitro

Addition of quisqualate to mouse hippocampal neurons in vitro elicited two types of changes in [Ca²⁺](i) as assessed by fura-2-based microfluorimetry. The first was a transient spike or group of oscillations and the second was a long lasting 'plateau' response. The long-lasting response was abolished on removal of either Ca²⁺ or Na⁺ from the external medium or by blocking voltage-sensitive Ca²⁺ channels. Furthermore, the novel glutamate antagonist 6-nitro-7-cyano-quinoxaline-2,3-dione was competitive inhibitor of this response. In contrast, none of these manipulations abolished the transient [Ca²⁺](i) spike. Transient [Ca²⁺](i) spikes of oscillations could also be produced by the α₁-adrenergic agonist phenylephrine. Production of such an α₁-response reduced the size of a subsequently elicited quisqualate response. However production of transient [Ca²⁺](i) spikes with caffeine did not alter the size of the quisqualate-induced spike. We conclude that hippocampal neurons possess two different types of quisqualate receptors. The first mediates quisqualate-induced depolarization and the second mediates Ca²⁺ mobilization from intracellular stores.