Using whole cell patch-clamp technique and immunocytochemistry on adult dorsal unpaired median (DUM) neurons isolated from the cockroach Periplaneta americana central nervous system, we reported the characterization of a native mGluR, sharing pharmacological properties with vertebrate mGluRIII, that regulated voltage-dependent sodium current (INa). The global INa 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 named INa1 and INa2 for L-glutamate-sensitive and -insensitive sodium currents. L-glutamate selectively reduced INa1 via 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 INa1 via a Gi/o and a suspected Gs proteins. According to the activated signalling 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 INa1, 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.