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Up- and down-regulation of the mechano-gated K2P channel TREK-1 by PIP2 and other membrane phospholipids

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Abstract

TREK-1 is an unconventional K+ channel that is activated by both physical and chemical stimuli. In this study, we show that the inner leaflet membrane phospholipids, including PIP2, exert a mixed stimulatory and inhibitory effect on TREK-1. Intra-cellular phospholipids inhibit basal channel activity and activation by membrane stretch, intra-cellular acidosis and arachidonic acid. However, binding of endogenous negative inner leaflet phospholipids with poly-lysine reduces inhibition and reveals channel stimulation by exogenous intra-cellular phospholipids. A similar effect is observed with PI, PE, PS and PA, unlike DG, demonstrating that the phosphate at position 3 is required although the global charge of the molecule is not critical. Inhibition depends on the distal C-terminal domain that conditions channel mechano-sensitivity, but is independent of the positively charged PIP2 stimulatory site in the proximal C-terminal domain. This is, to our knowledge, the first report of an ion channel dually regulated by membrane phospholipids.

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References

  1. Bockenhauer D, Zilberberg N, Goldstein SA (2001) KCNK2: reversible conversion of a hippocampal potassium leak into a voltage-dependent channel. Nat Neurosci 4:486–491

    PubMed  CAS  Google Scholar 

  2. Chemin J, Girard C, Duprat F, Lesage F, Romey G, Lazdunski M (2003) Mechanisms underlying excitatory effects of group I metabotropic glutamate receptors via inhibition of 2P domain K+ channels. EMBO J 22:5403–5411

    Article  PubMed  CAS  Google Scholar 

  3. Chemin J, Patel AJ, Duprat F, Lauritzen I, Lazdunski M, Honoré E (2005) A phospholipid sensor controls mechanogating of the K+ channel TREK-1. EMBO J 24:44–53

    Article  PubMed  CAS  Google Scholar 

  4. Fink M, Duprat F, Lesage F, Reyes R, Romey G, Heurteaux C, Lazdunski M (1996) Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel. EMBO J 15:6854–6862

    PubMed  CAS  Google Scholar 

  5. Honoré E, Maingret F, Lazdunski M, Patel AJ (2002) An intracellular proton sensor commands lipid- and mechano-gating of the K+ channel TREK-1. EMBO J 21:2968–2976

    Article  PubMed  Google Scholar 

  6. Honoré E, Patel AJ, Chemin J, Suchyna T, Sachs F (2006) Desensitization of mechano-gated K2P channels. Proc Natl Acad Sci USA 103:6859–6864

    Article  PubMed  CAS  Google Scholar 

  7. Huang CL, Feng S, Hilgemann DW (1998) Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma. Nature 391:803–806

    Article  PubMed  CAS  Google Scholar 

  8. Kim Y, Gnatenco C, Bang H, Kim D (2001) Localization of TREK-2 K+ channel domains that regulate channel kinetics and sensitivity to pressure, fatty acids and pHi. Pflugers Arch 2001:952–960

    Article  CAS  Google Scholar 

  9. Lauritzen I, Chemin J, Honoré E, Jodar M, Guy N, Lazdunski M, Patel AJ (2005) Cross-talk between the mechano-gated K2P channel TREK-1 and the actin cytoskeleton. EMBO Rep 6:642–648

    Article  PubMed  CAS  Google Scholar 

  10. Lauritzen I, Zanzouri M, Honoré E, Duprat F, Ehrengruber MU, Lazdunski M, Patel AJ (2003) K+-dependent cerebellar granule neuron apoptosis: role of TASK leak K+ channels. J Biol Chem 278:32068–32076

    Article  PubMed  CAS  Google Scholar 

  11. Lesage F (2003) Pharmacology of neuronal background potassium channels. Neuropharmacology 44:1–7

    Article  PubMed  CAS  Google Scholar 

  12. Lesage F, Lazdunski M (2000) Molecular and functional properties of two-pore-domain potassium channels. Am J Physiol Renal Physiol 279:F793–F801

    PubMed  CAS  Google Scholar 

  13. Lopes CM, Rohacs T, Czirjak G, Balla T, Enyedi P, Logothetis DE (2005) PIP2 hydrolysis underlies agonist-induced inhibition and regulates voltage gating of two-pore domain K+ channels. J Physiol 564:117–129

    Article  PubMed  CAS  Google Scholar 

  14. Maingret F, Fosset M, Lesage F, Lazdunski M, Honoré E (1999) TRAAK is a mammalian neuronal mechano-gated K+ channel. J Biol Chem 274:1381–1387

    Article  PubMed  CAS  Google Scholar 

  15. Maingret F, Honoré E, Lazdunski M, Patel AJ (2002) Molecular basis of the voltage-dependent gating of TREK-1, a mechano-sensitive K+ channel. Biochem Biophys Res Commun 292:339–346

    Article  PubMed  CAS  Google Scholar 

  16. Maingret F, Patel AJ, Lesage F, Lazdunski M, Honoré E (1999) Mechano- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel. J Biol Chem 274:26691–26696

    Article  PubMed  CAS  Google Scholar 

  17. Moore AL, Roe MW, Melnick RF, Lidofsky SD (2002) Calcium mobilization evoked by hepatocellular swelling is linked to activation of phospholipase Cgamma. J Biol Chem 277:34030–34035

    Article  PubMed  CAS  Google Scholar 

  18. Murbartian J, Lei Q, Sando JJ, Bayliss DA (2005) Sequential phosphorylation mediates receptor- and kinase-induced inhibition of TREK-1 background potassium channels. J Biol Chem 280:30175–30184

    Article  PubMed  CAS  Google Scholar 

  19. Patel AJ, Honoré E (2001) Anesthetic-sensitive 2P domain K+ channels. Anesthesiology 95:1013–1025

    Article  PubMed  CAS  Google Scholar 

  20. Patel AJ, Honoré E (2001) Properties and modulation of mammalian 2P domain K+ channels. Trends Neurosci 24:339–346

    Article  PubMed  CAS  Google Scholar 

  21. Patel AJ, Honoré E, Maingret F, Lesage F, Fink M, Duprat F, Lazdunski M (1998) A mammalian two pore domain mechano-gated S-like K+ channel. EMBO J 17:4283–4290

    Article  PubMed  CAS  Google Scholar 

  22. Patel AJ, Lazdunski M, Honoré E (2001) Lipid and mechano-gated 2P domain K+ channels. Curr Opin Cell Biol 13:422–428

    Article  PubMed  CAS  Google Scholar 

  23. Ruwhof C, van Wamel JT, Noordzij LA, Aydin S, Harper JC, van der Laarse A (2001) Mechanical stress stimulates phospholipase C activity and intracellular calcium ion levels in neonatal rat cardiomyocytes. Cell Calcium 29:73–83

    Article  PubMed  CAS  Google Scholar 

  24. Sachs F, Morris CE (1998) Mechanosensitive ion channels in nonspecialized cells. Rev Physiol Biochem Pharmacol 132:1–77

    Article  PubMed  CAS  Google Scholar 

  25. Sandoz G, Thummler S, Duprat F, Feliciangeli S, Vinh J, Escoubas P, Guy N, Lazdunski M, Lesage F (2006) AKAP150, a switch to convert mechano-, pH- and arachidonic acid-sensitive TREK K+ channels into open leak channels. EMBO J 25:5864–5872

    Article  PubMed  CAS  Google Scholar 

  26. Sheetz MP, Singer SJ (1974) Biological membranes as bilayer couples. A molecular mechanism of drug–erythocyte interactions. Proc Natl Acad Sci USA 71:4457–4461

    Article  PubMed  CAS  Google Scholar 

  27. Suchyna TM, Sachs F (2007) Mechanosensitive channel properties and membrane mechanics in mouse dystrophic myotubes. J Physiol (in press)

  28. Suchyna TM, Tape SE, Koeppe RE 2nd, Andersen OS, Sachs F, Gottlieb PA (2004) Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide enantiomers. Nature 430:235–240

    Article  PubMed  CAS  Google Scholar 

  29. Voets T, Nilius B (2003) TRPs make sense. J Membr Biol 192:1–8

    Article  PubMed  CAS  Google Scholar 

  30. Zhang H, He C, Yan X, Mirshahi T, Logothetis DE (1999) Activation of inwardly rectifying K+ channels by distinct PtdIns(4,5)P2 interactions. Nat Cell Biol 1:183–188

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by the CNRS, the FRM, l’ARC, la Ligue contre le cancer, the Fondation Paul Hamel and the ANR COD 2005. Martine Jodar is acknowledged for the expert technical assistance.

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Authors and Affiliations

  1. Institut de Génomique Fonctionnelle, UPR 2580 CNRS, 141 rue de la Cardonille, 34094, Montpellier cedex 05, France

    Jean Chemin

  2. Institut de Pharmacologie Moléculaire et Cellulaire, UMR 6097 CNRS, 660 route des Lucioles, 06560, Valbonne, France

    Amanda Jane Patel, Fabrice Duprat, Michel Lazdunski & Eric Honore

  3. Single Molecule Biophysics, University at Buffalo, State University of New York, 301 Cary Hall, Buffalo, NY, 14214, USA

    Frederick Sachs

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  1. Jean Chemin
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  2. Amanda Jane Patel
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  3. Fabrice Duprat
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  4. Frederick Sachs
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  5. Michel Lazdunski
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  6. Eric Honore
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Correspondence to Eric Honore.

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Chemin, J., Patel, A.J., Duprat, F. et al. Up- and down-regulation of the mechano-gated K2P channel TREK-1 by PIP2 and other membrane phospholipids. Pflugers Arch - Eur J Physiol 455, 97–103 (2007). https://doi.org/10.1007/s00424-007-0250-2

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  • DOI: https://doi.org/10.1007/s00424-007-0250-2

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