Lysophosphatidic acid induces a sustained elevation of neuronal intracellular calcium

Frederick W. Holtsberg, Marion R. Steiner, Katsutoshi Furukawa, Jeffrey N. Keller, Mark P. Mattson, Sheldon M. Steiner

Research output: Contribution to journalArticle

Abstract

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 ([Ca2+](i)). This increase is specific, in that the related lipids phosphatidic acid and lysophosphatidylcholine did not induce an alteration in [Ca2+](i). Moreover, consistent with a receptor-mediated process, there was no further increase in [Ca2+](i) after a second addition of LPA. The LPA-induced increase in [Ca2+](i) required extracellular calcium. However, studies with Cd2+, Ni2+, 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 [Ca2+](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 Mg2+ block of the NMDA receptors and lead to glutamate stimulation of an influx of calcium via NMDA receptors.

Original languageEnglish (US)
Pages (from-to)68-75
Number of pages8
JournalJournal of Neurochemistry
Volume69
Issue number1
StatePublished - Jul 1997
Externally publishedYes

Keywords

  • Glutamate receptors
  • Intracellular calcium concentration
  • Lysophosphatidic acid
  • Neurons

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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  • Cite this

    Holtsberg, F. W., Steiner, M. R., Furukawa, K., Keller, J. N., Mattson, M. P., & Steiner, S. M. (1997). Lysophosphatidic acid induces a sustained elevation of neuronal intracellular calcium. Journal of Neurochemistry, 69(1), 68-75.