METABOTROPIC GLUTAMATE GROUP-II RECEPTORS ACTIVATE A G-PROTEIN-COUPLED INWARDLY RECTIFYING K+ CURRENT IN NEURONS OF THE RAT CEREBELLUM

1.The effects of the group II metabotropic glutamate receptor (mGluR) agonists DCQ-IV and LY354740 were examined in neurones freshly dissoci ated from the rat cerebellum and olfactory bulb, using the whole-cell configuration of the patch-clamp technique. 2. Under experimental cond itions in which K+ currents would be insward, rapid application of DCG -IV and LY354740 to interneurones expressing the group II mGluRs induc ed an inward current in a subpopulation of interneurones of the cerebe llum, the unipolar brush cells. 3. The currents induced by DCG-IV and LY354740 had the major characteristics of a G protein-coupled inwardly rectifying K+ channel (GIRK) current; namely, rapid activation and de activation upon agonist application and removal, G protein dependence, strong inward rectification, Cs+ and Ba2+ sensitivity, and K+ selecti vity. 4. In Golgi cells of the cerebellum and interneurones of the acc essory olfactory bulb, which also express group II mGluRs, LY354740 di d not induce GIRK activation but inhibited voltage-gated Ca2+ channel currents. 5. These results demonstrate that, in unipolar brush cells, native group II mGluRs can functionally couple to activation of GIRKs. Thus, the absence of coupling in the majority of CNS neurones examine d to date may be due to restricted cellular co-localization or coexpre ssion of the appropriate proteins.