Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1995 Dec 15;489(Pt 3):701–707. doi: 10.1113/jphysiol.1995.sp021084

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

M Bünemann 1, B Brandts 1, D M zu Heringdorf 1, C J van Koppen 1, K H Jakobs 1, L Pott 1
PMCID: PMC1156840  PMID: 8788935

Abstract

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.

Full text

PDF
705

Images in this article

704Figure 3
on p.704
705Figure 4
on p.705

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Banach K., Bünemann M., Hüser J., Pott L. Serum contains a potent factor that decreases beta-adrenergic receptor-stimulated L-type Ca2+ current in cardiac myocytes. Pflugers Arch. 1993 May;423(3-4):245–250. doi: 10.1007/BF00374402. [DOI] [PubMed] [Google Scholar]
  2. Banach K., Hüser J., Lipp P., Wellner M. C., Pott L. Activation of muscarinic K+ current in guinea-pig atrial myocytes by a serum factor. J Physiol. 1993 Feb;461:263–281. doi: 10.1113/jphysiol.1993.sp019513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bünemann M., Pott L. Membrane-delimited activation of muscarinic K current by an albumin-associated factor in guinea-pig atrial myocytes. Pflugers Arch. 1993 Nov;425(3-4):329–334. doi: 10.1007/BF00374183. [DOI] [PubMed] [Google Scholar]
  4. Clapham D. E. Direct G protein activation of ion channels? Annu Rev Neurosci. 1994;17:441–464. doi: 10.1146/annurev.ne.17.030194.002301. [DOI] [PubMed] [Google Scholar]
  5. Desai N. N., Zhang H., Olivera A., Mattie M. E., Spiegel S. Sphingosine-1-phosphate, a metabolite of sphingosine, increases phosphatidic acid levels by phospholipase D activation. J Biol Chem. 1992 Nov 15;267(32):23122–23128. [PubMed] [Google Scholar]
  6. Durieux M. E., Salafranca M. N., Lynch K. R., Moorman J. R. Lysophosphatidic acid induces a pertussis toxin-sensitive Ca(2+)-activated Cl- current in Xenopus laevis oocytes. Am J Physiol. 1992 Oct;263(4 Pt 1):C896–C900. doi: 10.1152/ajpcell.1992.263.4.C896. [DOI] [PubMed] [Google Scholar]
  7. Ghosh T. K., Bian J., Gill D. L. Sphingosine 1-phosphate generated in the endoplasmic reticulum membrane activates release of stored calcium. J Biol Chem. 1994 Sep 9;269(36):22628–22635. [PubMed] [Google Scholar]
  8. Goodemote K. A., Mattie M. E., Berger A., Spiegel S. Involvement of a pertussis toxin-sensitive G protein in the mitogenic signaling pathways of sphingosine 1-phosphate. J Biol Chem. 1995 Apr 28;270(17):10272–10277. doi: 10.1074/jbc.270.17.10272. [DOI] [PubMed] [Google Scholar]
  9. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  10. Jalink K., van Corven E. J., Moolenaar W. H. Lysophosphatidic acid, but not phosphatidic acid, is a potent Ca2(+)-mobilizing stimulus for fibroblasts. Evidence for an extracellular site of action. J Biol Chem. 1990 Jul 25;265(21):12232–12239. [PubMed] [Google Scholar]
  11. Kurachi Y., Nakajima T., Sugimoto T. Short-term desensitization of muscarinic K+ channel current in isolated atrial myocytes and possible role of GTP-binding proteins. Pflugers Arch. 1987 Oct;410(3):227–233. doi: 10.1007/BF00580270. [DOI] [PubMed] [Google Scholar]
  12. Mattie M., Brooker G., Spiegel S. Sphingosine-1-phosphate, a putative second messenger, mobilizes calcium from internal stores via an inositol trisphosphate-independent pathway. J Biol Chem. 1994 Feb 4;269(5):3181–3188. [PubMed] [Google Scholar]
  13. Premont R. T., Inglese J., Lefkowitz R. J. Protein kinases that phosphorylate activated G protein-coupled receptors. FASEB J. 1995 Feb;9(2):175–182. doi: 10.1096/fasebj.9.2.7781920. [DOI] [PubMed] [Google Scholar]
  14. Sakmann B., Noma A., Trautwein W. Acetylcholine activation of single muscarinic K+ channels in isolated pacemaker cells of the mammalian heart. Nature. 1983 May 19;303(5914):250–253. doi: 10.1038/303250a0. [DOI] [PubMed] [Google Scholar]
  15. Tigyi G., Henschen A., Miledi R. A factor that activates oscillatory chloride currents in Xenopus oocytes copurifies with a subfraction of serum albumin. J Biol Chem. 1991 Nov 5;266(31):20602–20609. [PubMed] [Google Scholar]
  16. Wang Y. G., Lipsius S. L. Acetylcholine potentiates acetylcholine-induced increases in K+ current in cat atrial myocytes. Am J Physiol. 1995 Mar;268(3 Pt 2):H1313–H1321. doi: 10.1152/ajpheart.1995.268.3.H1313. [DOI] [PubMed] [Google Scholar]
  17. Wu J., Spiegel S., Sturgill T. W. Sphingosine 1-phosphate rapidly activates the mitogen-activated protein kinase pathway by a G protein-dependent mechanism. J Biol Chem. 1995 May 12;270(19):11484–11488. doi: 10.1074/jbc.270.19.11484. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES