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Modulation by Ionotropic Excitatory Amino Acids and Potassium of (±)‐1‐Aminocyclopentane‐ trans ‐1,3‐Dicarboxylic Acid‐Stimulated Phosphoinositide Hydrolysis in Mouse Cerebellar Granule Cells
Author(s) -
Gorman Adrienne M.,
Grieve Angus,
Griffiths Roger
Publication year - 1995
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.1471-4159.1995.65062473.x
Subject(s) - acpd , ampa receptor , metabotropic receptor , ionotropic effect , nmda receptor , metabotropic glutamate receptor , glutamate receptor , excitatory postsynaptic potential , chemistry , biophysics , kainate receptor , biology , biochemistry , receptor
The effect of ionotropic excitatory amino acids and potassium on the formation of inositol phosphates elicited by the metabotropic glutamate receptor agonist (±)‐1‐aminocyclopentane‐ trans ‐1,3‐dicarboxylic acid ( trans ‐ACPD) was studied in mouse cerebellar granule cells. In Mg 2+ ‐containing buffers, NMDA (50–100 µ M ), α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA; 10–1,000 µ M ), and high potassium (10–30 m M ) enhanced synergistically the response to a maximally effective concentration of 500 µ M trans ‐ACPD. Potentiation of the trans ‐ACPD response was blocked by higher concentrations of NMDA (>500 µ M ) and potassium (>35 m M ) but not by AMPA (up to 1 m M ). The potentiation by NMDA of the trans ‐ACPD‐stimulated phosphoinositide hydrolysis was blocked by d,l ‐2‐amino‐5‐phosphonopentanoic acid (APV), a competitive NMDA‐receptor antagonist. Under Mg 2+ ‐free conditions, the accumulation of inositol phosphates in the presence of trans ‐ACPD alone was equal to that attained by trans ‐ACPD in Mg 2+ ‐containing buffers when costimulated with maximally enhancing concentrations of NMDA (50 µ M ). trans ‐ACPD potentiated synergistically the NMDA‐evoked increases in cytosolic free‐Ca 2+ levels in Mg 2+ ‐containing but not in Mg 2+ ‐free solutions, and moreover did not enhance the AMPA‐evoked increases in cytosolic free‐Ca 2+ levels. The calcium ionophore A23187 caused a dose‐dependent increase in inositol phosphate accumulation but did not enhance the response stimulated by trans ‐ACPD alone. These results demonstrate the existence of cross talk between metabotropic and ionotropic glutamate receptors in cerebellar granule cells. The exact mechanism remains unclear but appears to involve interplay of G protein‐coupled phospholipase C activation and regulated elevation of cytosolic free‐Ca 2+ levels. This study may provide a framework for future investigations at the cellular and molecular level that clarify the functional relevance and molecular mechanisms that are described.