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This Article Full Text Full Text (PDF) All Versions of this Article: 96/5/2437    most recent 00588.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lavialle-Defaix, C. Articles by Grolleau, F. Search for Related Content PubMed PubMed Citation Articles by Lavialle-Defaix, C. Articles by Grolleau, F.

Differential Regulation of Two Distinct Voltage-Dependent Sodium Currents by Group III Metabotropic Glutamate Receptor Activation in Insect Pacemaker Neurons

¹Laboratoire Récepteurs et Canaux Ioniques Membranaires, Unité Propre de Recherche et de l'Enseignement Supérieur, Equipe d’Accueil 2647, Université d'Angers, Unité de Formation et de Recherche (UFR) Sciences and ²Laboratoire Biologie Intégrée Neurovasculaire, Unité Mixte de Recherche, Centre National de la Recherche Scientifique 6214/Institut National de la Santé et de la Recherche Médicale 771, UFR Sciences Médicales, Angers, France

Submitted 6 June 2006; accepted in final form 3 August 2006

Using whole cell patch-clamp technique and immunocytochemistry on adult dorsal unpaired median (DUM) neurons isolated from the cockroach Periplaneta americana CNS, we reported the characterization of a native mGluR, sharing pharmacological properties with vertebrate metabotropic glutamate receptor III (mGluRIII) that regulated voltage-dependent sodium current (I_Na). The global I_Na was dissociated by means of L-glutamate sensitivity, deactivation time constant, voltage dependence of activation and inactivation, recovery from inactivation, and intracellular regulation process. These two currents were respectively designated I_Na1 and I_Na2 for L-glutamate-sensitive and -insensitive sodium currents. L-glutamate selectively reduced I_Na1 by an increase of intracellular cAMP level. Using different activators and/or inhibitors of G proteins and cAMP/PKA cascade, together with St-Ht31 (an inhibitor of PKA binding to AKAP) and AKAP-79 antibodies, we established that mGluRIII was linked to I_Na1 by a Gi/o and a suspected Gs protein. According to the activated signaling pathway, L-glutamate elevated the cAMP level, which thereby activated cytosolic PKA and released PKA bound to AKAP. As expected from both biophysical and pharmacological studies, we showed that, through an inhibition of I_Na1, L-glutamate increased DUM neuron spontaneous electrical activity. These results indicated that such mGluRIII-activated dual processes provided a new physiological control of pacemaker neuronal firing.