Dual signaling by mGluR5a results in bi-directional modulation of N-type Ca2+ channels.
We have studied how N-type Ca2+ channels are modulated by the metabotropic glutamate receptor 5a (mGluR5a) in Xenopus oocytes. Stimulation of the receptor with glutamate initiated two parallel responses, a rapid inhibition followed by an upregulation of the Ca2+ current. Although a subsequent stimulation did not upregulate the Ca2+ current, it did still produce a reduction in the amplitude of the current. The upregulation of Ca2+ channels was prevented by the protein kinases inhibitor staurosporine and it was mimicked by the activation of PKC with phorbol esters. In contrast, the inhibition of the Ca2+ current was insensitive to staurosporine. These results show that mGluR5a exerts a bi-directional influence on Ca2+ channels, which may explain how group I mGluRs facilitate and inhibit glutamate release at central synapses.
Sánchez-Prieto
J
J
Instituto Cajal, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain. jsprieto@vet.ucm.es
Paternain
A V
AV
Lerma
J
J
D000818:Animals; D001464:Barium / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D005260:Female; D007700:Kinetics; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D037342:Pertussis Toxin / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D014982:Xenopus laevis
D020864:Calcium Channels, N-Type; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D001464:Barium; D015240:Phorbol 12,13-Dibutyrate; D037342:Pertussis Toxin