Group II metabotropic glutamate receptors inhibit cAMP-dependent protein kinase-mediated enhancement 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.