Tyrosine kinase-dependent suppression of a potassium channel by the G protein-coupled m1 muscarinic acetylcholine receptor

Cell. 1993 Dec 17;75(6):1145-56. doi: 10.1016/0092-8674(93)90324-j.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / metabolism
  • Calcimycin / pharmacology
  • Calcium / metabolism
  • Cell Line
  • Embryo, Mammalian
  • Embryo, Nonmammalian
  • Female
  • GTP-Binding Proteins / biosynthesis
  • GTP-Binding Proteins / metabolism*
  • Genistein
  • Humans
  • Isoflavones / pharmacology
  • Kidney
  • Kinetics
  • Membrane Potentials
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Myocardium / metabolism
  • Neuroblastoma
  • Oocytes / physiology
  • Potassium Channel Blockers
  • Potassium Channels / biosynthesis
  • Potassium Channels / metabolism*
  • Protein Kinase C / metabolism
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism*
  • Receptors, Muscarinic / biosynthesis
  • Receptors, Muscarinic / metabolism*
  • Signal Transduction
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transfection
  • Tumor Cells, Cultured
  • Xenopus

Substances

  • Isoflavones
  • Potassium Channel Blockers
  • Potassium Channels
  • Receptors, Muscarinic
  • Calcimycin
  • Genistein
  • Protein-Tyrosine Kinases
  • Protein Kinase C
  • GTP-Binding Proteins
  • Tetradecanoylphorbol Acetate
  • Calcium