G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons.
To study the role of G protein-coupled, inwardly rectifying K+ (GIRK) channels in mediating neurotransmitter actions in hippocampal neurons, we have examined slices from transgenic mice lacking the GIRK2 gene. The outward currents evoked by agonists for GABA(B) receptors, 5HT1A receptors, and adenosine A1 receptors were essentially absent in mutant mice, while the inward current evoked by muscarinic receptor activation was unaltered. In contrast, the presynaptic inhibitory action of a number of presynaptic receptors on excitatory and inhibitory terminals was unaltered in mutant mice. These included GABA(B), adenosine, muscarinic, metabotropic glutamate, and NPY receptors on excitatory synapses and GABA(B) and opioid receptors on inhibitory synapses. These findings suggest that a number of G protein-coupled receptors activate the same class of postsynaptic K+ channel, which contains GIRK2. In addition, the GIRK2 channels play no role in the inhibition mediated by presynaptic G protein-coupled receptors, suggesting that the same receptor can couple to different effector systems according to its subcellular location in the neuron.
Lüscher
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C
Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143, USA.
Jan
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Stoffel
M
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Malenka
R C
RC
Nicoll
R A
RA
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D015536:Down-Regulation / Q000502:physiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018755:GABA Agonists / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D017729:Presynaptic Terminals / Q000737:chemistry* / Q000378:metabolism; D017966:Pyramidal Cells / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D013570:Synaptic Membranes / Q000737:chemistry* / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology
D000700:Analgesics; D004745:Enkephalins; D018691:Excitatory Amino Acid Antagonists; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018755:GABA Agonists; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D018340:Receptors, Adrenergic, alpha-1; D018080:Receptors, GABA-B; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D019204:GTP-Binding Proteins; D001418:Baclofen