Metabotropic glutamate group II receptors activate a G protein-coupled inwardly rectifying K+ current in neurones of the rat cerebellum.
1. The effects of the group II metabotropic glutamate receptor (mGluR) agonists DCG-IV and LY354740 were examined in neurones freshly dissociated from the rat cerebellum and olfactory bulb, using the whole-cell configuration of the patch-clamp technique. 2. Under experimental conditions in which K+ currents would be inward, rapid application of DCG-IV and LY354740 to interneurones expressing the group II mGluRs induced an inward current in a subpopulation of interneurones of the cerebellum, 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 deactivation upon agonist application and removal, G protein dependence, strong inward rectification, Cs+ and Ba2+ sensitivity, and K+ selectivity. 4. In Golgi cells of the cerebellum and interneurones of the accessory olfactory bulb, which also express group II mGluRs, LY354740 did 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 examined to date may be due to restricted cellular co-localization or co-expression of the appropriate proteins.
Knoflach
F
F
Preclinical CNS Research, Pharmaceuticals Division, F. Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland.
Kemp
J A
JA
D000818:Animals; D001464:Barium / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002531:Cerebellum / Q000502:physiology*; D003521:Cyclopropanes / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009830:Olfactory Bulb / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*
D001643:Bridged Bicyclo Compounds; D015220:Calcium Channels; D003521:Cyclopropanes; D018690:Excitatory Amino Acid Agonists; D015221:Potassium Channels; D018094:Receptors, Metabotropic Glutamate; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D001464:Barium; D019204:GTP-Binding Proteins; C104753:eglumetad; D002118:Calcium; D005998:Glycine