Medical Journals

Differential Regulation of Two Distinct Voltage-dependent Sodium Currents by Group Iii Metabotropic Glutamate Receptor Activation in Insect Pacemaker Neurons.

Authors:
  • Lavialle-Defaix Céline
  • Gautier Hélène
  • Defaix Antoine
  • Lapied Bruno
  • Grolleau Françoise

From: Laboratoire Récepteurs et Canaux Ioniques Membranaires, UPRES EA 2647, Université d’Angers, UFR Sciences, 2 Boulevard Lavoisier, F-49045 Angers cedex, France.

Journal of neurophysiology

  • Publish Date: Nov 2006
  • ISSN: 0022-3077
  • Volume: 96
  • Issue: 5
  • Pages: 2437-50
  • Medium: Print
  • Language: English
  • Citation (JAMA): Lavialle-Defaix Céline, Gautier Hélène, Defaix Antoine, et al. Differential Regulation of Two Distinct Voltage-dependent Sodium Currents by Group Iii Metabotropic Glutamate Receptor Activation in Insect Pacemaker Neurons.. J. Neurophysiol. Nov 2006;96:2437-50

Abstract

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.

Mesh Headings (Keywords): Algorithms, Animals, Biological Clocks, Calcium Channel Blockers, Cell Separation, Cyclic AMP, Electrophysiology, Forskolin, Glutamic Acid, Immunohistochemistry, Ion Channel Gating, Male, Membrane Potentials, Neurons, Patch-Clamp Techniques, Periplaneta, Pertussis Toxin, Potassium Channel Blockers, Receptors, Metabotropic Glutamate, Signal Transduction, Sodium Channels


Check for Full Text / PubMed Unique Identifier (PMID): 16899636


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