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Lysophosphatidic Acid Induces a Sustained Elevation of Neuronal Intracellular Calcium
Author(s) -
Holtsberg Frederick W.,
Steiner Marion R.,
Furukawa Katsutoshi,
Keller Jeffrey N.,
Mattson Mark P.,
Steiner Sheldon M.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.69010068.x
Subject(s) - kainate receptor , ampa receptor , lysophosphatidic acid , glutamate receptor , nmda receptor , calcium , chemistry , calcium in biology , receptor , medicine , endocrinology , sgk1 , extracellular , biology , microbiology and biotechnology , biochemistry , kinase
Lysophosphatidic acid (LPA) is a lipid biomediator enriched in the brain. A novel LPA‐induced response in rat hippocampal neurons is described herein, namely, a rapid and sustained elevation in the concentration of free intracellular calcium ([Ca 2+ ] i ). This increase is specific, in that the related lipids phosphatidic acid and lysophosphatidylcholine did not induce an alteration in [Ca 2+ ] i . Moreover, consistent with a receptor‐mediated process, there was no further increase in [Ca 2+ ] i after a second addition of LPA. The LPA‐induced increase in [Ca 2+ ] i required extracellular calcium. However, studies with Cd 2+ , Ni 2+ , and nifedipine and nystatin‐perforated patch clamp analyses did not indicate involvement of voltage‐gated calcium channels in the LPA‐induced response. In contrast, glutamate appears to have a significant role in the LPA‐induced increase in [Ca 2+ ] i , because this increase was inhibited by NMDA receptor antagonists and α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA)/kainate receptor antagonists. Thus, LPA treatment may result in an increased extracellular glutamate concentration that could stimulate AMPA/kainate receptors and thereby alleviate the Mg 2+ block of the NMDA receptors and lead to glutamate stimulation of an influx of calcium via NMDA receptors.