Acute- and long-term glutamate-mediated regulation of [Ca++](i) in rat hippocampal pyramidal neurons in vitro

S. R. Glaum, W. K. Scholz, R. J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

We used a fura 2-based digital imaging technique to analyze the effects of glutamate (GLU) and GLU agonists on intracellular free calcium ([Ca++](i)) in cultures of rat hippocampal pyramidal neurons. Depolarization of cells with 50 mM K+ raised [Ca++](i) in all parts of the cell (e.g., soma and dendrites). [Ca++](i) was also increased in these cells by GLU, kainate, quisqualate, N-methyl-D-aspartate (NMDA) and caffeine (CAF). Multiple challenges of a neuron with GLU gave rise to high 'plateau' levels of [Ca++](i) that were maintained over the entire length of an experiment (up to 1 hr). In the presence of the NMDA receptor antagonist 2-amino-5-phosphonovalerate multiple applications of GLU only produced multiple transient increases in [Ca++](i). Multiple challenges of a cell with NMDA (0 Mg++, 1 μM glycine) also produced maintained plateau responses in [Ca++](i). Multiple challenges with kainate or quisqualate only produced multiple transient responses in [Ca++](i). Plateau responses induced by GLU or NMDA could be reversibly reduced by removal of extracellular Ca++. Co++ and Ni++ (500 μM) also reduced the magnitude of the plateau, but nitrendipine and tetrodotoxin were generally ineffective. The kinase inhibitor staurosporine also reversibly reduced the magnitude of the plateau. The initiation of a [Ca++](i) plateau could be blocked by 2-amino-5-phosphonovalerate although this compound was ineffective at reducing a plateau once it had formed. Thus, activation of NMDA receptors in these neurons leads to a maintained influx of Ca++ that could be responsible for certain long-term effects of GLU.

Original languageEnglish (US)
Pages (from-to)1293-1302
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume253
Issue number3
StatePublished - 1990

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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