Activation of muscarinic K+ current in guinea-pig atrial myocytes by sphingosine-1-phosphate.
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.
Bünemann
M
M
Institut für Physiologie, Ruhr-Universität Bochum, Germany.
Brandts
B
B
zu Heringdorf
D M
DM
van Koppen
C J
CJ
Jakobs
K H
KH
Pott
L
L
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008246:Lysophospholipids; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010743:Phospholipids / Q000097:blood; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D002317:Cardiovascular Agents; D008246:Lysophospholipids; D018721:Muscarinic Agonists; D010743:Phospholipids; D015221:Potassium Channels; C060506:sphingosine 1-phosphate; D019204:GTP-Binding Proteins; D000241:Adenosine; D000109:Acetylcholine; D013110:Sphingosine