Permissive effect of voltage on mGlu 7 receptor subtype signaling in neurons.
G protein-coupled receptors mobilize neuronal signaling cascades which until now have not been shown to depend on the state of membrane depolarization. Thus we have previously shown that the metabotropic glutamate receptor type 7 (mGlu7 receptor) blocks P/Q-type Ca(2+) channels via activation of a G(o) protein and PKC, in cerebellar granule cells. We show here that the transient depolarizations used to evoke the studied Ca(2+) current were indeed permissive to activate this pathway by a mGlu7 receptor agonist. Indeed, sustained depolarization to 0 mV was sufficient to inhibit P/Q-type Ca(2+) channels. This effect involved a conformational change in voltage-gated sodium channel independently of Na(+) flux, activation of a pertussis toxin-sensitive G-protein, inositol trisphosphate formation, intracellular Ca(2+) release, and PKC activity. Subliminal sustained membrane depolarization became efficient in inducing inositol trisphosphate formation, release of intracellular Ca(2+) and in blocking Ca(2+) channels, when applied concomitantly with the mGlu7a receptor agonist, d,l-aminophosphonobutyrate. This synergistic effect of membrane depolarization and mGlu7 receptor activation provides a mechanism by which neuronal excitation could control action of the mGlu7 receptor in neurons.
Perroy
Julie
J
CNRS-UPR 9023 CCIPE and CNRS-UPR 1142 IGH, 141 Rue de la Cardonille, 34094 Montpellier, Cedex 05, France.
Richard
Sylvain
S
Nargeot
Joel
J
Bockaert
Joel
J
Fagni
Laurent
L
D000818:Animals; D001464:Barium / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000378:metabolism*; D020907:Calcium Channels, Q-Type / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D008564:Membrane Potentials; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D020033:Protein Isoforms / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015398:Signal Transduction; D015222:Sodium Channels / Q000378:metabolism; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D020033:Protein Isoforms; D018094:Receptors, Metabotropic Glutamate; D015222:Sodium Channels; D010566:Virulence Factors, Bordetella; C102719:metabotropic glutamate receptor 7; D001464:Barium; D037342:Pertussis Toxin; D011493:Protein Kinase C; C070515:bisindolylmaleimide I