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Journal of Neuroscience, Vol 12, 4358-4371, Copyright © 1992 by Society for Neuroscience
Inhibition of calcium channels in rat CA3 pyramidal neurons by a metabotropic glutamate receptor
KJ Swartz and BP Bean
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
L-Glutamate rapidly and reversibly suppressed Ca channel current in freshly
dissociated pyramidal neurons from the CA3 region of the rat hippocampus.
L-Glutamate inhibition of Ca channel current could be distinguished from
activation of background conductance by appropriate ionic conditions and by
distinct pharmacological profiles. Ca channel inhibition by glutamate was
mimicked by quisqualate, ibotenate, racemict-ACPD and 1S,3R-ACPD but not by
kainate, AMPA, L-aspartate, NMDA, L-2-amino-4-phosphonobutyric acid, or
1R,3S-ACPD; 6-cyano-7- nitroquinoxaline-2,3-dione did not inhibit the
response. All agonists inhibited a similar fraction of
high-voltage-activated Ca channel current, typically approximately 30%.
Concentration-response relations for the agonists were consistent with
mediation by a metabotropic glutamate receptor. The stereospecific agonist
1S,3R-ACPD was especially useful since it did not activate background
conductances. The fraction of Ca channel current sensitive to 1S,3R-ACPD
was partially blocked by omega-conotoxin GVIA but was not sensitive to
dihydropyridine antagonists or agonists. The suppression of Ca channels by
1S,3R-ACPD became irreversible when cells were dialyzed with GTP- gamma-S.
1S,3R-ACPD suppressed Ca channel currents in outside-out membrane patches
but not in cell-attached patches when applied outside the patch. These
results suggest that metabotropic glutamate receptors suppress the activity
of N-type Ca channels in CA3 neurons by a mechanism involving G-proteins
but not readily diffusible second messengers.
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