Article date: 1988/11/1
PubMed ID: 2856095
Journal name: Proceedings of the National Academy of Sciences of the United States of America (ISSN: 0027-8424)
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.
Author List: Murphy S N, Miller R J
Publication Types: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
Substances mentioned in the article: Glutamates; Oxadiazoles; Receptors, Glutamate; Receptors, Neurotransmitter; Ibotenic Acid; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Quisqualic Acid; Kainic Acid; Calcium;
Mesh terms: Animals; Calcium/metabolism; Cells, Cultured; Embryo, Mammalian; Glutamates/physiology; Hippocampus/metabolism; Ibotenic Acid/analogs & derivatives; Kainic Acid/pharmacology; Kinetics; Mice; Mice, Inbred C57BL; Neurons/drug effects; Oxadiazoles/pharmacology; Quisqualic Acid; Receptors, Glutamate; Receptors, Neurotransmitter/physiology; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;
Citations: - 2469180