Tyrosine kinase-dependent suppression of a potassium channel by the G protein-coupled m1 muscarinic acetylcholine receptor.
Neurotransmitter receptors alter membrane excitability and synaptic efficacy by generating intracellular signals that ultimately change the properties of ion channels. Through expression studies in Xenopus oocytes and mammalian cells, we found that the G protein-coupled m1 muscarinic acetylcholine receptor potently suppresses a cloned delayed rectifier K+ channel through a pathway involving phospholipase C activation and direct tyrosine phosphorylation of the K+ channel. Furthermore, analysis of neuroblastoma cells revealed that a similar tyrosine kinase-dependent pathway links endogenous G protein-coupled receptors to suppression of the native RAK channel. These results suggest a novel mechanism by which neurotransmitters and hormones may regulate a specific type of K+ channel that is widely expressed in the mammalian brain and heart.
Huang
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Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138.
Morielli
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Peralta
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D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D005260:Female; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D019833:Genistein; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D007668:Kidney; D007700:Kinetics; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009206:Myocardium / Q000378:metabolism; D009447:Neuroblastoma; D009865:Oocytes / Q000502:physiology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000096:biosynthesis / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014981:Xenopus
D007529:Isoflavones; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D000001:Calcimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium