METABOTROPIC GLUTAMATE RECEPTORS ACTIVATE G-PROTEIN-COUPLED INWARDLY RECTIFYING POTASSIUM CHANNELS IN XENOPUS OOCYTES

Receptor-mediated activation of a G-protein-coupled inwardly rectifyin g potassium channel (GIRK) is a common mechanism for synaptic modulati on in the CNS. However, evidence for metabotropic glutamate receptor ( mGluR) activation of GIRK is virtually nonexistent, despite the widesp read and overlapping distribution of these proteins. We examined this apparent paradox by coexpressing mGluRs 1a, 2, and 7 with the GIRK sub units Kir3.1 and Kir3.4 in Xenopus oocytes. Functional expression of G IRK was confirmed by coexpression with the D2 dopamine receptor that i s known to activate GIRK in neurons. Agonist activation of each of the three mGluRs evoked inward potassium currents in symmetrical KCI solu tions. The current amplitudes evoked by mGluR1a, mGluR2, and D2 were c omparable, whereas mGluR7 currents were somewhat smaller. mGluR1a-evok ed GIRK currents were not blocked in BAPTA-treated oocytes, demonstrat ing that GIRK activation was distinct from phospholipase C-mediated ac tivation of the endogenous calcium-dependent chloride current (I-CaCl) . Pertussis toxin (PTX) treatment significantly reduced both the mGluR and D2 receptor-evoked GIRK currents. In oocytes in which mGluR2 and D2 were coexpressed, activation of mGluR2 occluded additional D2 recep tor current, indicating-that mGluR2 and D2 receptor coupling to GIRK i nvolves a common G-protein. The efficient coupling of mGluRs to GIRK i n oocytes suggests either that mGluR activation of GIRK has been overl ooked in neurons or possibly that mGluRs are excluded from GIRK-contai ning microdomains.