Differential regulation of two distinct voltage-dependent sodium currents by group III metabotropic glutamate receptor activation in insect pacemaker neurons

作者：Lavialle Defaix Celine; Gautier Helene; Defaix Antoine; Lapied Bruno^*; Grolleau Francoise

来源：Journal of Neurophysiology, 2006, 96(5): 2437-2450.

DOI：10.1152/jn.00588.2006

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.

• 出版日期2006-11