Activation of muscarinic K+ current in guinea-pig atrial myocytes by sphingosine-1-phosphate

J Physiol. 1995 Dec 15;489 ( Pt 3)(Pt 3):701-7. doi: 10.1113/jphysiol.1995.sp021084.


1. Activation of muscarinic K+ current (IK(ACh)) by sphingosine-1-phosphate (Sph-1-P) was studied in isolated cultured guinea-pig atrial myocytes using whole-cell voltage clamp. 2. Sph-1-P caused activation of IK(ACh) with an EC50 of 1.2 nM. The maximal current that could be activated by Sph-1-P amounted to about 90% of the IK(ACh) caused by a saturating concentration of acetylcholine (ACh, 10 microM). Sphingosine (1 microM), which can mimic the signalling effects of Sph-1-P in other cells, failed to cause measurable activation of IK(ACh). 3. IK(ACh) activation by Sph-1-P was completely suppressed in cells treated with pertussis toxin. 4. Desensitization of muscarinic receptors by pre-incubation of the cells with carbachol did not affect the response to Sph-1-P; likewise, pre-incubation of the cells with Sph-1-P resulted in a reduced sensitivity to the phospholipid but not to ACh. In contrast, pre-incubation with either Sph-1-P or a serum phospholipid previously described as activating atrial IK(ACh) resulted in reduced sensitivity to both phospholipids. 5. It is concluded that activation of IK(ACh) by Sph-1-P in atrial myocytes is induced by binding to a novel G protein-coupled phospholipid receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Adenosine / pharmacology
  • Animals
  • Biotransformation / drug effects
  • Cardiovascular Agents / pharmacology
  • Female
  • GTP-Binding Proteins / metabolism
  • Guinea Pigs
  • Heart / drug effects
  • In Vitro Techniques
  • Lysophospholipids*
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Muscarinic Agonists / pharmacology*
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Patch-Clamp Techniques
  • Phospholipids / blood
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology


  • Cardiovascular Agents
  • Lysophospholipids
  • Muscarinic Agonists
  • Phospholipids
  • Potassium Channels
  • sphingosine 1-phosphate
  • GTP-Binding Proteins
  • Adenosine
  • Acetylcholine
  • Sphingosine