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Activation of muscarinic K+ current in guinea‐pig atrial myocytes by sphingosine‐1‐phosphate.
Author(s) -
Bünemann M,
Brandts B,
zu Heringdorf D M,
van Koppen C J,
Jakobs K H,
Pott L
Publication year - 1995
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1995.sp021084
Subject(s) - sphingosine 1 phosphate , muscarinic acetylcholine receptor , atrial myocytes , guinea pig , chemistry , medicine , myocyte , biophysics , acetylcholine , sphingosine , endocrinology , cardiology , biology , receptor
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.