A glutamate receptor regulates Ca2+ mobilization in hippocampal neurons.
We investigated the effect of various excitatory amino acids on intracellular free Ca2+ concentration ( [Ca2+]i) in single mouse hippocampal neurons in vitro by using the Ca2+-sensitive dye fura-2. In normal physiological solution, glutamate, kainate, N-methyl-D-aspartate, and quisqualate all produced increases in [Ca2+]i. When all extracellular Ca2+ was removed, kainate and N-methyl-D-aspartate were completely ineffective, but quisqualate and glutamate were able to produce a spike-like Ca2+ transient, presumably reflecting the release of Ca2+ from intracellular stores. Ca2+ transients of similar shape could also be produced by the alpha 1-adrenergic agonist phenylephrine. After the production of a Ca2+ transient a second addition of quisqualate was ineffective unless intracellular stores were refilled by loading the cell with Ca2+ following depolarization in Ca2+-containing medium. None of the conventional excitatory amino acid receptor antagonists inhibited the Ca2+-mobilizing effects of quisqualate. Furthermore alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) was unable to produce Ca2+ mobilization in Ca2+-free medium, although it could produce Ca2+ influx in Ca2+-containing medium. Thus, glutamate can produce mobilization of Ca2+ from intracellular stores in hippocampal neurons by acting on a quisqualate-sensitive but AMPA-insensitive receptor. This receptor is therefore distinct from the quisqualate receptor that produces cell depolarization. The possibility that this Ca2+-mobilizing effect is mediated by inositol triphosphate production is discussed.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005971:Glutamates / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology; D016318:Quisqualic Acid; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D005971:Glutamates; D010069:Oxadiazoles; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D007608:Kainic Acid; D002118:Calcium