Pflügers Archiv - European Journal of Physiology

, Volume 455, Issue 6, pp 1097–1103 | Cite as

Revisiting TRPC1 and TRPC6 mechanosensitivity

  • Philip Gottlieb
  • Joost Folgering
  • Rosario Maroto
  • Albert Raso
  • Thomas G. Wood
  • Alex Kurosky
  • Charles Bowman
  • Delphine Bichet
  • Amanda Patel
  • Frederick Sachs
  • Boris Martinac
  • Owen P. HamillEmail author
  • Eric Honoré
Ion Channels


This article addresses whether TRPC1 or TRPC6 is an essential component of a mammalian stretch-activated mechano-sensitive Ca2+ permeable cation channel (MscCa). We have transiently expressed TRPC1 and TRPC6 in African green monkey kidney (COS) or Chinese hamster ovary (CHO) cells and monitored the activity of the stretch-activated channels using a fast pressure clamp system. Although both TRPC1 and TRPC6 are highly expressed at the protein level, the amplitude of the mechano-sensitive current is not significantly altered by overexpression of these subunits. In conclusion, although several TRPC channel members, including TRPC1 and TRPC6, have been recently proposed to form MscCa in vertebrate cells, the functional expression of these TRPC subunits in heterologous systems remains problematic.


Mechano-electrical transduction Cardiovascular response Cation channel Mechanosensitive channel Mechanoreceptor 



JF, DB, AP, and EH are grateful to the ANR 2005 Cardiovasculaire-obésité-diabète; to the Association for Information and Research on Genetic Kidney Disease, France; to the Fondation del Duca; to the Fondation de France; to the Fondation de la Recherche Médicale; to EU Marie-Curie fellowships, to INSERM; to Human Frontier Science program; and to Centre National de la Recherche Scientifique for support. RM and OH thank the Department of Defense Prostate Cancer Research Program and the National Cancer Institute for their support. The Buffalo group was supported by the NIH and the Oshei Foundation. AR and BM thank the Australian Research Council for support. We are grateful to Wade J. Sigurdson, Director of the Confocal Microscope, and three-dimensional Imaging Facility at UB, and Leoncio Vergara of the Optical Imaging Laboratory (UTMB) for help with imaging.

Supplementary material


  1. 1.
    Alloui A, Zimmermann K, Mamet J, Duprat F, Noel J, Chemin J, Guy N, Blondeau N, Voilley N, Rubat-Coudert C, Borsotto M, Romey G, Heurteaux C, Reeh P, Eschalier A, Lazdunski M (2006) TREK-1, a K+channel involved in polymodal pain perception. EMBO J 25:2368–2376PubMedCrossRefGoogle Scholar
  2. 2.
    Beech DJ (2005) TRPC1: store-operated channel and more. Pflugers Arch 451:53–60PubMedCrossRefGoogle Scholar
  3. 3.
    Bode F, Sachs F, Franz MR (2001) Tarantula peptide inhibits atrial fibrillation. Nature 409:35–36PubMedCrossRefGoogle Scholar
  4. 4.
    Christensen AP, Corey DP (2007) TRP channels in mechanosensation: direct or indirect activation? Nat Rev Neurosci 8:510–521PubMedCrossRefGoogle Scholar
  5. 5.
    Corey DP (2006) What is the hair cell transduction channel? J Physiol 576:23–28PubMedCrossRefGoogle Scholar
  6. 6.
    Corey DP, Garcia-Anoveros J, Holt JR, Kwan KY, Lin SY, Vollrath MA, Amalfitano A, Cheung EL, Derfler BH, Duggan A, Geleoc GS, Gray PA, Hoffman MP, Rehm HL, Tamasauskas D, Zhang DS (2004) TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells. Nature 432:723–730PubMedCrossRefGoogle Scholar
  7. 7.
    Dietrich A, Mederos YSM, Gollasch M, Gross V, Storch U, Dubrovska G, Obst M, Yildirim E, Salanova B, Kalwa H, Essin K, Pinkenburg O, Luft FC, Gudermann T, Birnbaumer L (2005) Increased vascular smooth muscle contractility in TRPC6−/− mice. Mol Cell Biol 25:6980–6989PubMedCrossRefGoogle Scholar
  8. 8.
    Dietrich A, Kalwa H, Storch U, Mederos YSM, Salanova B, Pinkenburg O, Dubrovska G, Essin K, Gollasch M, Birnbaumer L, Gudermann T (2007) Pressure-induced and store-operated cation influx in vascular smooth muscle cells is independent of TRPC1. Pflugers Arch DOI  10.1007/s00424-007-0314-3
  9. 9.
    Guharay F, Sachs F (1984) Stretch-activated single ion channel currents in tissue-cultured embryonic chick skeletal muscle. J Physiol 352:685–701PubMedGoogle Scholar
  10. 10.
    Hamill OP, Maroto R (2007) TRPCs as MS channels. Curr Top Membr 59:191–231Google Scholar
  11. 11.
    Hofmann T, Obukhov AG, Schaefer M, Harteneck C, Gudermann T, Schultz G (1999) Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature 397:259–263PubMedCrossRefGoogle Scholar
  12. 12.
    Hofmann T, Schaefer M, Schultz G, Gudermann T (2002) Subunit composition of mammalian transient receptor potential channels in living cells. Proc Natl Acad Sci U S A 99:7461–7466PubMedCrossRefGoogle Scholar
  13. 13.
    Honoré E (2007) The neuronal background K2P channels: focus on TREK-1. Nat Rev Neurosci 8:251–261PubMedCrossRefGoogle Scholar
  14. 14.
    Honoré E, Patel AJ, Chemin J, Suchyna T, Sachs F (2006) Desensitization of mechano-gated K2P channels. Proc Natl Acad Sci U S A 103:6859–6864PubMedCrossRefGoogle Scholar
  15. 15.
    Kindt KS, Viswanath V, Macpherson L, Quast K, Hu H, Patapoutian A, Schafer WR (2007) Caenorhabditis elegans TRPA-1 functions in mechanosensation. Nat Neurosci 10:568–577PubMedCrossRefGoogle Scholar
  16. 16.
    Lauritzen I, Chemin J, Honoré E, Jodar M, Guy N, Lazdunski M, Jane Patel A (2005) Cross-talk between the mechano-gated K2P channel TREK-1 and the actin cytoskeleton. EMBO Rep 6:642–648PubMedCrossRefGoogle Scholar
  17. 17.
    Levina N, Totemeyer S, Stokes NR, Louis P, Jones MA, Booth IR (1999) Protection of Escherichia coli cells against extreme turgor by activation of MscS and MscL mechanosensitive channels: identification of genes required for MscS activity. EMBO J 18:1730–1737PubMedCrossRefGoogle Scholar
  18. 18.
    Maroto R, Hamill OP (2007) MscCa regulation of tumor cell migration and metastasis. Curr Top Membr 59:485–509CrossRefGoogle Scholar
  19. 19.
    Maroto R, Raso A, Wood TG, Kurosky A, Martinac B, Hamill OP (2005) TRPC1 forms the stretch-activated cation channel in vertebrate cells. Nat Cell Biol 7:179–185PubMedCrossRefGoogle Scholar
  20. 20.
    Morris CE (1990) Mechanosensitive ion channels. J Membr Biol 113:93–107PubMedCrossRefGoogle Scholar
  21. 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 17:4283–4290PubMedCrossRefGoogle Scholar
  22. 22.
    Pedersen SA, Nilius B (2007) Transient receptor potential channels in mechanosensing and cell volume regulation. Methods Enzymol 428:183–207PubMedCrossRefGoogle Scholar
  23. 23.
    Sachs F (1997) Mechanical transduction by ion channels: how forces reach the channel. Soc Gen Physiol Ser 52:209–218PubMedGoogle Scholar
  24. 24.
    Sachs F, Morris CE (1998) Mechanosensitive ion channels in nonspecialized cells. Rev Physiol Biochem Pharmacol 132:1–77PubMedGoogle Scholar
  25. 25.
    Spassova MA, Hewavitharana T, Xu W, Soboloff J, Gill DL (2006) A common mechanism underlies stretch activation and receptor activation of TRPC6 channels. Proc Natl Acad Sci U S A 103:16586–16591PubMedCrossRefGoogle Scholar
  26. 26.
    Strubing C, Krapivinsky G, Krapivinsky L, Clapham DE (2001) TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron 29:645–655PubMedCrossRefGoogle Scholar
  27. 27.
    Sukharev SI, Blount P, Martinac B, Blattner FR, Kung C (1994) A large-conductance mechanosensitive channel in E. coli encoded by mscL alone. Nature 368:265–268PubMedCrossRefGoogle Scholar
  28. 28.
    Villereal ML (2006) Mechanism and functional significance of TRPC channel multimerization. Semin Cell Dev Biol 17:618–629PubMedCrossRefGoogle Scholar
  29. 29.
    Welsh DG, Morielli AD, Nelson MT, Brayden JE (2002) Transient receptor potential channels regulate myogenic tone of resistance arteries. Circ Res 90:248–250PubMedCrossRefGoogle Scholar
  30. 30.
    Wilkinson NC, Gao F, Hamill OP (1998) Effects of mechano-gated cation channel blockers on Xenopus oocyte growth and development. J Membr Biol 165:161–174PubMedCrossRefGoogle Scholar
  31. 31.
    Zhang Y, Gao F, Popov VL, Wen JW, Hamill OP (2000) Mechanically gated channel activity in cytoskeleton-deficient plasma membrane blebs and vesicles from Xenopus oocytes. J Physiol 523(Pt 1):117–130PubMedCrossRefGoogle Scholar
  32. 32.
    Zhou X, Su Z, Anishkin A, Friske EM, Loukin SH, Kung C, Saimi Y (2007) Yeast screens show aromatic residues at the end of the sixth helix anchor transient receptor potential gate. Proc Natl Acad Sci USA 104:15555–15559PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Philip Gottlieb
    • 1
  • Joost Folgering
    • 2
  • Rosario Maroto
    • 3
  • Albert Raso
    • 4
  • Thomas G. Wood
    • 5
  • Alex Kurosky
    • 5
  • Charles Bowman
    • 1
  • Delphine Bichet
    • 2
  • Amanda Patel
    • 2
  • Frederick Sachs
    • 1
  • Boris Martinac
    • 6
  • Owen P. Hamill
    • 3
    Email author
  • Eric Honoré
    • 2
  1. 1.Single Molecule BiophysicsSUNYBuffaloUSA
  2. 2.IPMC-CNRS, UMR 6097Université de Nice-Sophia AntipolisValbonneFrance
  3. 3.Department of Neuroscience & Cell BiologyUTMBGalvestonUSA
  4. 4.School of Medicine and PharmacologyUniversity of Western AustraliaCrawleyAustralia
  5. 5.Department of Biochemistry and Molecular BiologyUTMBGalvestonUSA
  6. 6.School of Biomedical SciencesUniversity of QueenslandBrisbaneAustralia

Personalised recommendations