Group II metabotropic glutamate receptors inhibit cAMP-dependent protein kinase-mediated enhancemednt of tetrodotoxin-resistant sodium currents in mouse dorsal root ganglion neurons.
Tetrodotoxin (TTX)-resistant sodium currents are important in nociception and nociceptive sensitization, which is partially due to their cAMP/protein kinase A (PKA)-mediated enhancement. Here we studied the effects of group II mGluR activation on TTX-resistant sodium currents in cultured mouse dorsal root ganglion (DRG) neurons. Activation of adenylyl cyclase with forskolin caused an increase in the amplitude of TTX-R currents and a leftward shift of the activation curve. When neurons were treated with ammonium pyrrolidinedithiocarbamate (APDC), a selective group II mGluR agonist, both the forskolin-induced increase in current amplitude and the shift of activation curve were blocked. LY341495, a group II mGluR antagonist, prevented these inhibitory effects of APDC. Our results suggest that group II mGluRs can negatively regulate TTX-R sodium currents in mouse DRG neurons.
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
Dongni
D
Yang
Robert W
RW
Gereau
D000596:Amino Acids / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology* / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D011759:Pyrrolidines / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology*; D013859:Thiocarbamates / Q000494:pharmacology; D013997:Time Factors; D014966:Xanthenes / Q000494:pharmacology
D000596:Amino Acids; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009479:Neuropeptides; D011759:Pyrrolidines; D018094:Receptors, Metabotropic Glutamate; C503479:Scn9a protein, mouse; D015222:Sodium Channels; D013859:Thiocarbamates; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; D005576:Colforsin; C020972:pyrrolidine dithiocarbamic acid; D017868:Cyclic AMP-Dependent Protein Kinases