Quisqualate receptor-mediated depression of calcium currents in hippocampal neurons

The modulation of Ca²⁺ currents by the excitatory neurotransmitter glutamate and its analogs was investigated in hippocampal neurons in culture. In the presence of glutamate receptor-gated ion channel antagonists, all of the analogs tested caused either a small reversible depression or had no effect on the Ca²⁺ current. However, in neurons dialyzed with GTPyS, quisqualate and glutamate but not NMDA, kainate, AMPA, or l-APB caused marked and irreversible depressions of the Ca²⁺ current. This inhibition was only observed if Ca²⁺ was present in either the internal or external medium. Intracellular H-7, staurosporine, IP₃, cAMP, cGMP, or calmodulin inhibitors failed to prevent the quisqualate-induced Ca²⁺ current inhibition. These observations are consistent with an interaction between a G protein-coupled glutamate receptor and Ca²⁺ channels.