Metabotropic glutamate receptors activate G-protein-coupled inwardly rectifying potassium channels in Xenopus oocytes.
Receptor-mediated activation of a G-protein-coupled inwardly rectifying potassium channel (GIRK) is a common mechanism for synaptic modulation in the CNS. However, evidence for metabotropic glutamate receptor (mGluR) activation of GIRK is virtually nonexistent, despite the widespread and overlapping distribution of these proteins. We examined this apparent paradox by coexpressing mGluRs 1a, 2, and 7 with the GIRK subunits Kir3.1 and Kir3.4 in Xenopus oocytes. Functional expression of GIRK was confirmed by coexpression with the D2 dopamine receptor that is known to activate GIRK in neurons. Agonist activation of each of the three mGluRs evoked inward potassium currents in symmetrical KCI solutions. The current amplitudes evoked by mGluR1a, mGluR2, and D2 were comparable, whereas mGluR7 currents were somewhat smaller. mGluR1a-evoked GIRK currents were not blocked in BAPTA-treated oocytes, demonstrating that GIRK activation was distinct from phospholipase C-mediated activation of the endogenous calcium-dependent chloride current (lCaCl). 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 receptor current, indicating that mGluR2 and D2 receptor coupling to GIRK involves a common G-protein. The efficient coupling of mGluRs to GIRK in oocytes suggests either that mGluR activation of GIRK has been overlooked in neurons or possibly that mGluRs are excluded from GIRK-containing microdomains.
Saugstad
J A
JA
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201, USA.
Segerson
T P
TP
Westbrook
G L
GL
D000818:Animals; D001696:Biomechanical Phenomena; D004594:Electrophysiology; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis
D015221:Potassium Channels; D018094:Receptors, Metabotropic Glutamate; D019204:GTP-Binding Proteins