Pflügers Archiv - European Journal of Physiology

, Volume 467, Issue 10, pp 2121–2140 | Cite as

Homodimeric anoctamin-1, but not homodimeric anoctamin-6, is activated by calcium increases mediated by the P2Y1 and P2X7 receptors

  • Michaela Stolz
  • Manuela Klapperstück
  • Thomas Kendzierski
  • Silvia Detro-dassen
  • Anna Panning
  • Günther Schmalzing
  • Fritz MarkwardtEmail author
Ion channels, receptors and transporters


The P2X7 receptor (P2X7R) is a ligand-gated ion channel that conducts Na+, K+, and Ca2+ when activated by extracellular ATP. In various cell types, such as secretory epithelia, the P2X7R is co-expressed with Ca2+-dependent Cl channels of the TMEM16/anoctamin family. Here, we studied whether the P2X7R and TMEM16A/anoctamin-1 (Ano1) or TMEM16F/anoctamin-6 (Ano6) interact functionally and physically, using oocytes of Xenopus laevis and Ambystoma mexicanum (Axolotl) for heterologous expression. As a control, we co-expressed anoctamin-1 with the P2Y1 receptor (P2Y1R), which induces the release of Ca2+ from intracellular stores via activating phospholipase C through coupling to Gαq. We found that co-expression of anoctamin-1 with the P2Y1R resulted in a small transient increase in Cl conductance in response to ATP. Co-expression of anoctamin-1 with the P2X7R resulted in a large sustained increase in Cl conductance via Ca2+ influx through the ATP-opened P2X7R in Xenopus and in Axolotl oocytes, which lack endogenous Ca2+-dependent Cl channels. P2Y1R- or P2X7R-mediated stimulation of Ano1 was primarily functional, as demonstrated by the absence of a physically stable interaction between Ano1 and the P2X7R. In the pancreatic cell line AsPC-1, we found the same functional Ca2+-dependent interaction of P2X7R and Ano1. The P2X7R-mediated sustained activation of Ano1 may be physiologically relevant to the time course of stimulus-secretion coupling in secretory epithelia. No such increase in Cl conductance could be elicited by activating the P2X7 receptor in either Xenopus oocytes or Axolotl oocytes co-expressing Ano6. The lack of function of Ano6 can, at least in part, be explained by its poor cell-surface expression, resulting from a relatively inefficient exit of the homodimeric Ano6 from the endoplasmic reticulum.


Anoctamin-1 Anoctamin-6 P2X7 receptor Quaternary structure Intracellular Ca2+ 



We would like to thank the Deutsche Forschungsgemeinschaft (Ma1581/15-3; Schm536/9-3) for their financial support. We would also like to thank GlaxoSmithKline for their permission to use the monoclonal antibody against the hP2X7R ectodomain, Prof. Dr. Friedrich Koch-Nolte of University Medical Center, Hamburg for providing us with the corresponding hybridoma cell line, and Prof. Dr. Barbara Seliger, Institute for Medical Immunology of the Martin-Luther-University Halle for providing us the AsPC-1 cell line.

Ethical standards

The experiments comply with the current laws of Germany.

Supplementary material

424_2015_1687_Fig13_ESM.gif (35 kb)
Fig. S1

ADP-induced mP2Y1-dependent activation of mANO1. Experiments were performed in Ca-ORi using the same protocol as described in the legend to Fig. 3b (GIF 35 kb)

424_2015_1687_MOESM1_ESM.tif (903 kb)
High-resolution image (TIFF 903 kb)


  1. 1.
    Adinolfi E, Cirillo M, Woltersdorf R, Falzoni S, Chiozzi P, Pellegatti P, Callegari MG, Sandona D, Markwardt F, Schmalzing G, Di Virgilio F (2010) Trophic activity of a naturally occurring truncated isoform of the P2X7 receptor. FASEB J 24:3393–3404CrossRefPubMedGoogle Scholar
  2. 2.
    Adinolfi E, Pizzirani C, Idzko M, Panther E, Norgauer J, Di Virgilio F, Ferrari D (2005) P2X7 receptor: death or life? Purinergic Signal 1:219–227PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Allbritton NL, Meyer T, Stryer L (1992) Range of messenger action of calcium ion and inositol 1,4,5-trisphosphate. Science 258:1812–1815CrossRefPubMedGoogle Scholar
  4. 4.
    Alonso-Torre SR, Trautmann A (1993) Calcium responses elicited by nucleotides in macrophages—interaction between two receptor subtypes. J Biol Chem 268:18640–18647PubMedGoogle Scholar
  5. 5.
    Amedee T, Despeyroux S (1995) ATP activates cationic and anionic conductances in Schwann cells cultured from dorsal root ganglia of the mouse. Proc R Soc Lond B 259:277–284CrossRefGoogle Scholar
  6. 6.
    Arreola J, Melvin JE (2003) A novel chloride conductance activated by extracellular ATP in mouse parotid acinar cells. J Physiol Lond 547:197–208PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Becker D, Woltersdorf R, Boldt W, Schmitz S, Braam U, Schmalzing G, Markwardt F (2008) The P2X7 carboxyl tail is a regulatory module of P2X7 receptor channel activity. J Biol Chem 283:25725–25734CrossRefPubMedGoogle Scholar
  8. 8.
    Boldt W, Klapperstück M, Büttner C, Sadtler S, Schmalzing N, Markwardt F (2003) Glu496Ala polymorphism of human P2X7 receptor does not affect its electrophysiological phenotype. Am J Physiol 284:C749–C756CrossRefGoogle Scholar
  9. 9.
    Boton R, Dascal N, Gillo B, Lass Y (1989) Two calcium-activated chloride conductances in Xenopus laevis oocytes permeabilized with the ionophore A23187. J Physiol Lond 408:511–534PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Bretschneider F, Klapperstück M, Löhn M, Markwardt F (1995) Nonselective cationic currents elicited by extracellular ATP in human B-lymphocytes. Pflugers Arch 429:691–698CrossRefPubMedGoogle Scholar
  11. 11.
    Browne LE, Compan V, Bragg L, North RA (2013) P2X7 receptor channels allow direct permeation of nanometer-sized dyes. J Neurosci 33:3557–3566CrossRefPubMedGoogle Scholar
  12. 12.
    Brunner JD, Lim NK, Schenck S, Duerst A, Dutzler R (2014) X-ray structure of a calcium-activated TMEM16 lipid scramblase. Nature 516:207–212CrossRefPubMedGoogle Scholar
  13. 13.
    Buell G, Chessell IP, Michel AD, Colo G, Salazzo M, Herren S, Gretener D, Grahames C, Kaur R, Kosco-Vilbois MH, Humphrey PPA (1998) Blockade of human P2X7 receptor function with a monoclonal antibody. Blood 92:3521–3528PubMedGoogle Scholar
  14. 14.
    Caputo A, Caci E, Ferrera L, Pedemonte N, Barsanti C, Sondo E, Pfeffer U, Ravazzolo R, Zegarra-Moran O, Galietta LJ (2008) TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity. Science 322:590–594CrossRefPubMedGoogle Scholar
  15. 15.
    Cervetto C, Alloisio S, Frattaroli D, Mazzotta MC, Milanese M, Gavazzo P, Passalacqua M, Nobile M, Maura G, Marcoli M (2013) The P2X7 receptor as a route for non-exocytotic glutamate release: dependence on the carboxyl tail. J Neurochem 124:821–831CrossRefPubMedGoogle Scholar
  16. 16.
    Colomar A, Amedee T (2001) ATP stimulation of P2X7 receptors activates three different ionic conductances on cultured mouse Schwann cells. Eur J Neurosci 14:927–936CrossRefPubMedGoogle Scholar
  17. 17.
    Detro-Dassen S, Schanzler M, Lauks H, Martin I, zu Berstenhorst SM, Nothmann D, Torres-Salazar D, Hidalgo P, Schmalzing G, Fahlke C (2008) Conserved dimeric subunit stoichiometry of SLC26 multifunctional anion exchangers. J Biol Chem 283:4177–4188CrossRefPubMedGoogle Scholar
  18. 18.
    Di Virgilio F (2007) Liaisons dangereuses: P2X7 and the inflammasome. Trends Pharmacol Sci 28:465–472CrossRefPubMedGoogle Scholar
  19. 19.
    Di Virgilio F, Ferrari D, Adinolfi E (2009) P2X7: a growth-promoting receptor-implications for cancer. Purinergic Signal 5:251–256PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Duan SM, Anderson CM, Keung EC, Chen YM, Chen YR, Swanson RA (2003) P2X7 receptor-mediated release of excitatory amino acids from astrocytes. J Neurosci 23:1320–1328PubMedGoogle Scholar
  21. 21.
    Duran C, Qu Z, Osunkoya AO, Cui Y, Hartzell HC (2012) ANOs 3–7 in the anoctamin/mem16 Cl channel family are intracellular proteins. Am J Physiol 302:C482–C493CrossRefGoogle Scholar
  22. 22.
    Egan TM, Khakh BS (2004) Contribution of calcium ions to P2X channel responses. J Neurosci 24:3413–3420CrossRefPubMedGoogle Scholar
  23. 23.
    Erdahl WL, Chapman CJ, Taylor RW, Pfeiffer DR (1994) Ca2+ transport properties of ionophores A23187, ionomycin, and 4-BrA23187 in a well defined model system. Biophys J 66:1678–1693PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Fallah G, Römer T, Braam U, Detro-Dassen S, Markwardt F, Schmalzing G (2011) TMEM16A(a)/anoctamin-1 shares a homodimeric architecture with CLC chloride channels. Mol Cell Proteomics. doi: 10.1074/mcp.M110.004697 PubMedCentralPubMedGoogle Scholar
  25. 25.
    Faria RX, Reis R, Casabulho CM, Alberto AP, Fernando DP, Henriques-Pons A, Alves LA (2009) Pharmacological properties of a pore induced by raising intracellular Ca2+. Am J Physiol 297:C28–C42CrossRefGoogle Scholar
  26. 26.
    Flittiger B, Klapperstück M, Schmalzing G, Markwardt F (2010) Effects of protons on macroscopic and single-channel currents mediated by the human P2X7 receptor. Biochim Biophys Acta Biomembranes 1798:947–957CrossRefGoogle Scholar
  27. 27.
    Galietta LJV (2009) The TMEM16 protein family: a new class of chloride channels? Biophys J 97:3047–3053PubMedCentralCrossRefPubMedGoogle Scholar
  28. 28.
    Gendreau S, Voswinkel S, Torres-Salazar D, Lang N, Heidtmann H, Detro-Dassen S, Schmalzing G, Hidalgo P, Fahlke C (2004) A trimeric quaternary structure is conserved in bacterial and human glutamate transporters. J Biol Chem 279:39505–39512CrossRefPubMedGoogle Scholar
  29. 29.
    Gloor S, Pongs O, Schmalzing G (1995) A vector for the synthesis of cRNAs encoding Myc epitope-tagged proteins in Xenopus laevis oocytes. Gene 160:213–217CrossRefPubMedGoogle Scholar
  30. 30.
    Gomez-Hernandez JM, Stühmer W, Parekh AB (1997) Calcium dependence and distribution of calcium-activated chloride channels in Xenopus oocytes. J Physiol Lond 502:569–574PubMedCentralCrossRefPubMedGoogle Scholar
  31. 31.
    Griffon N, Buttner C, Nicke A, Kuhse J, Schmalzing G, Betz H (1999) Molecular determinants of glycine receptor subunit assembly. EMBO J 18:4711–4721PubMedCentralCrossRefPubMedGoogle Scholar
  32. 32.
    Grubb S, Poulsen KA, Juul CA, Kyed T, Klausen TK, Larsen EH, Hoffmann EK (2013) TMEM16F (Anoctamin 6), an anion channel of delayed Ca2+ activation. J Gen Physiol 141:585–600PubMedCentralCrossRefPubMedGoogle Scholar
  33. 33.
    Grudzien-Nogalska E, Stepinski J, Jemielity J, Zuberek J, Stolarski R, Rhoads RE, Darzynkiewicz E (2007) Synthesis of anti-reverse cap analogs (ARCAs) and their applications in mRNA translation and stability. Methods Enzymol 431:203–227CrossRefPubMedGoogle Scholar
  34. 34.
    Haeger S, Kuzmin D, Detro-Dassen S, Lang N, Kilb M, Tsetlin V, Betz H, Laube B, Schmalzing G (2010) An intramembrane aromatic network determines pentameric assembly of Cys-loop receptors. Nat Struct Mol Biol 17:90–98CrossRefPubMedGoogle Scholar
  35. 35.
    Hodges RR, Vrouvlianis J, Shatos MA, Dartt DA (2009) Characterization of P2X7 purinergic receptors and their function in rat lacrimal gland. Invest Ophthalmol Vis Sci 50:5681–5689PubMedCentralCrossRefPubMedGoogle Scholar
  36. 36.
    Huang F, Zhang H, Wu M, Yang H, Kudo M, Peters CJ, Woodruff PG, Solberg OD, Donne ML, Huang X, Sheppard D, Fahy JV, Wolters PJ, Hogan BL, Finkbeiner WE, Li M, Jan YN, Jan LY, Rock JR (2012) Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction. Proc Natl Acad Sci U S A 109:16354–16359PubMedCentralCrossRefPubMedGoogle Scholar
  37. 37.
    Hung AC, Chu YJ, Lin YH, Weng JY, Chen HB, Au YC, Sun SH (2005) Roles of protein kinase C in regulation of P2X7 receptor-mediated calcium signalling of cultured type-2 astrocyte cell line, RBA-2. Cell Signal 17:1384–1396CrossRefPubMedGoogle Scholar
  38. 38.
    Kim M, Jiang LH, Wilson HL, North RA, Surprenant A (2001) Proteomic and functional evidence for a P2X7 receptor signalling complex. EMBO J 20:6347–6358PubMedCentralCrossRefPubMedGoogle Scholar
  39. 39.
    King BF, Townsend-Nicholson A (2003) Nucleotide and nucleoside receptors. Tocris Rev 23:1–11Google Scholar
  40. 40.
    Klapperstück M, Büttner C, Böhm T, Schmalzing G, Markwardt F (2000) Characteristics of P2X7 receptors from human B lymphocytes expressed in Xenopus oocytes. Biochim Biophys Acta 1467:444–456CrossRefPubMedGoogle Scholar
  41. 41.
    Klapperstück M, Büttner C, Schmalzing G, Markwardt F (2001) Functional evidence of distinct ATP activation sites at the human P2X7 receptor. J Physiol Lond 534:25–35PubMedCentralCrossRefPubMedGoogle Scholar
  42. 42.
    Kmit A, van Kruchten R, Ousingsawat J, Mattheij NJ, Senden-Gijsbers B, Heemskerk JWM, Schreiber R, Bevers EM, Kunzelmann K (2013) Calcium-activated and apoptotic phospholipid scrambling induced by Ano6 can occur independently of Ano6 ion currents. Cell Death Dis 4:e611PubMedCentralCrossRefPubMedGoogle Scholar
  43. 43.
    Kubick C, Schmalzing G, Markwardt F (2011) The effect of anions on the human P2X7 receptor. Biochim Biophys Acta Biomembranes 1808:2913–2922CrossRefGoogle Scholar
  44. 44.
    Kunzelmann K, Nilius B, Owsianik G, Schreiber R, Ousingsawat J, Sirianant L, Wanitchakool P, Bevers EM, Heemskerk JWM (2013) Molecular functions of anoctamin 6 (TMEM16F): a chloride channel, cation channel, or phospholipid scramblase? Pflugers Arch 466:407–414CrossRefPubMedGoogle Scholar
  45. 45.
    Kunzelmann K, Tian Y, Martins JR, Faria D, Kongsuphol P, Ousingsawat J, Thevenod F, Roussa E, Rock J, Schreiber R (2011) Anoctamins. Pflugers Arch 426:195–208CrossRefGoogle Scholar
  46. 46.
    Kuruma A, Hartzell HC (1999) Dynamics of calcium regulation of chloride currents in Xenopus oocytes. Am J Physiol 276:C161–C175PubMedGoogle Scholar
  47. 47.
    Liu W, Lu M, Liu B, Huang Y, Wang K (2012) Inhibition of Ca2+-activated Cl channel ANO1/TMEM16A expression suppresses tumor growth and invasiveness in human prostate carcinoma. Cancer Lett 326:41–51CrossRefPubMedGoogle Scholar
  48. 48.
    Löhn M, Klapperstück M, Riemann D, Markwardt F (2001) Sodium block and depolarization diminish P2Z-dependent Ca2+ entry in human B lymphocytes. Cell Calcium 29:395–408CrossRefPubMedGoogle Scholar
  49. 49.
    Machaca K, Hartzell HC (1999) Reversible Ca gradients between the subplasmalemma and cytosol differentially activate Ca-dependent Cl currents. J Gen Physiol 113:249–266PubMedCentralCrossRefPubMedGoogle Scholar
  50. 50.
    Machaca K, Qu Z, Kuruma A, Hartzell HC, McCarty N (2002) The endogenous Ca-activated Cl channel in Xenopus oocytes: a physiologically and biophysicall rich model system. Curr Top Membr 53:3–39CrossRefGoogle Scholar
  51. 51.
    Mazzone A, Eisenman ST, Strege PR, Yao Z, Ordog T, Gibbons SJ, Farrugia G (2012) Inhibition of cell proliferation by a selective inhibitor of the Ca2+-activated Cl channel, Ano1. Biochem Biophys Res Commun 427:248–253PubMedCentralCrossRefPubMedGoogle Scholar
  52. 52.
    Mehta VB, Hart J, Wewers MD (2001) ATP-stimulated release of interleukin (IL)-1β and IL-18 requires priming by lipopolysaccharide and is independent of caspase-1 cleavage. J Biol Chem 276:3820–3826CrossRefPubMedGoogle Scholar
  53. 53.
    Nakamoto T, Brown DA, Catalan MA, Gonzalez-Begne M, Romanenko VG, Melvin JE (2009) Purinergic P2X7 receptors mediate ATP-induced saliva secretion by the mouse submandibular gland. J Biol Chem 284:4815–4822PubMedCentralCrossRefPubMedGoogle Scholar
  54. 54.
    Namkung W, Yao Z, Finkbeiner WE, Verkman AS (2011) Small-molecule activators of TMEM16A, a calcium-activated chloride channel, stimulate epithelial chloride secretion and intestinal contraction. FASEB J 25:4048–4062PubMedCentralCrossRefPubMedGoogle Scholar
  55. 55.
    Nicke A, Bäumert HG, Rettinger J, Eichele A, Lambrecht G, Mutschler E, Schmalzing G (1998) P2X1 and P2X3 receptors form stable trimers: a novel structural motiv of ligand-gated ion channels. EMBO J 17:3016–3028PubMedCentralCrossRefPubMedGoogle Scholar
  56. 56.
    Nicke A, Kuan YH, Masin M, Rettinger J, Marquez-Klaka B, Bender O, Gorecki DC, Murrell-Lagnado RD, Soto F (2009) A functional P2X7 splice variant with an alternative transmembrane domain 1 escapes gene inactivation in P2X7 KO mice. J Biol Chem 284:25813–25822PubMedCentralCrossRefPubMedGoogle Scholar
  57. 57.
    Nicke A, Thurau H, Sadtler S, Rettinger J, Schmalzing G (2004) Assembly of nicotinic α7 subunits in Xenopus oocytes is partially blocked at the tetramer level. FEBS Lett 575:52–58CrossRefPubMedGoogle Scholar
  58. 58.
    North RA (2002) Molecular physiology of P2X receptors. Physiol Rev 82:1013–1067CrossRefPubMedGoogle Scholar
  59. 59.
    Novak I (2011) Purinergic signalling in epithelial ion transport—regulation of secretion and absorption. Acta Physiol (Oxf ) 202:501–522CrossRefGoogle Scholar
  60. 60.
    Paukert M, Hidayat S, Gründer S (2002) The P2X7 receptor from Xenopus laevis: formation of a large pore in Xenopus oocytes. FEBS Lett 513:253–258CrossRefPubMedGoogle Scholar
  61. 61.
    Pelegrin P, Surprenant A (2006) Pannexin-1 mediates large pore formation and interleukin-1 release by the ATP-gated P2X7 receptor. EMBO J 25:5071–5082PubMedCentralCrossRefPubMedGoogle Scholar
  62. 62.
    Pellegatti P, Falzoni S, Pinton P, Rizzuto R, Di Virgilio F (2005) A novel recombinant plasma membrane-targeted luciferase reveals a new pathway for ATP secretion. Mol Biol Cell 16:3659–3665PubMedCentralCrossRefPubMedGoogle Scholar
  63. 63.
    Rais I, Karas M, Schagger H (2004) Two-dimensional electrophoresis for the isolation of integral membrane proteins and mass spectrometric identification. Proteomics 4:2567–2571CrossRefPubMedGoogle Scholar
  64. 64.
    Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50:413–492PubMedGoogle Scholar
  65. 65.
    Rassendren F, Buell GN, Virginio C, Collo G, North RA, Surprenant A (1997) The permeabilizing ATP receptor, P2X7—cloning and expression of a human cDNA. J Biol Chem 272:5482–5486CrossRefPubMedGoogle Scholar
  66. 66.
    Rath A, Deber CM (2013) Correction factors for membrane protein molecular weight readouts on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Anal Biochem 434:67–72CrossRefPubMedGoogle Scholar
  67. 67.
    Reyes JP, Perez-Cornejo P, Hernandez-Carballo CY, Srivastava A, Romanenko VG, Gonzalez-Begne M, Melvin JE, Arreola J (2008) Na+ modulates anion permeation and block of P2X7 receptors from mouse parotid glands. J Membr Biol 223:73–85PubMedCentralCrossRefPubMedGoogle Scholar
  68. 68.
    Riedel T, Lozinsky I, Schmalzing G, Markwardt F (2007) Kinetics of P2X7 receptor-operated single channels currents. Biophys J 92:2377–2391PubMedCentralCrossRefPubMedGoogle Scholar
  69. 69.
    Riedel T, Schmalzing G, Markwardt F (2007) Influence of extracellular monovalent cations on pore and gating properties of P2X7 receptor-operated single channels currents. Biophys J 93:846–858PubMedCentralCrossRefPubMedGoogle Scholar
  70. 70.
    Saiyed T, Paarmann I, Schmitt B, Haeger S, Sola M, Schmalzing G, Weissenhorn W, Betz H (2007) Molecular basis of gephyrin clustering at inhibitory synapses: role of G- and E-domain interactions. J Biol Chem 282:5625–5632CrossRefPubMedGoogle Scholar
  71. 71.
    Sauter DR, Novak I, Pedersen SF, Larsen EH, Hoffmann EK (2014) ANO1 (TMEM16A) in pancreatic ductal adenocarcinoma (PDAC). Pflugers Arch. doi: 10.1007/s00424-014-1598-8: PubMedCentralPubMedGoogle Scholar
  72. 72.
    Schmalzing G, Kroner S, Schachner M, Gloor S (1992) The adhesion molecule on glia (AMOG/beta 2) and alpha 1 subunits assemble to functional sodium pumps in Xenopus oocytes. J Biol Chem 267:20212–20216PubMedGoogle Scholar
  73. 73.
    Schmalzing G, Ruhl K, Gloor SM (1997) Isoform-specific interactions of Na, K-ATPase subunits are mediated via extracellular domains and carbohydrates. Proc Natl Acad Sci U S A 94:1136–1141PubMedCentralCrossRefPubMedGoogle Scholar
  74. 74.
    Schreiber R, Uliyakina I, Kongsuphol P, Warth R, Mirza M, Martins JR, Kunzelmann K (2010) Expression and function of epithelial anoctamins. J Biol Chem 285:7838–7845PubMedCentralCrossRefPubMedGoogle Scholar
  75. 75.
    Schroeder BC, Cheng T, Jan YN, Jan LY (2008) Expression cloning of TMEM16A as a calcium-activated chloride channel subunit. Cell 134:1019–1029PubMedCentralCrossRefPubMedGoogle Scholar
  76. 76.
    Schubert R (1996) Multiple ligand-ion solutions: a guide for solution preparation and computer program understanding. J Vasc Res 33:86–98CrossRefPubMedGoogle Scholar
  77. 77.
    Schwaller B (2010) Cytosolic Ca2+ buffers. Cold Spring Harb Perspect Biol 2:a004051PubMedCentralCrossRefPubMedGoogle Scholar
  78. 78.
    Shimizu T, Iehara T, Sato K, Fujii T, Sakai H, Okada Y (2013) TMEM16F is a component of a Ca2+-activated Cl channel but not a volume-sensitive outwardly rectifying Cl channel. Am J Physiol 304:C748–C759CrossRefGoogle Scholar
  79. 79.
    Solini A, Chiozzi P, Morelli A, Fellin R, Di Virgilio F (1999) Human primary fibroblasts in vitro express a purinergic P2X7 receptor counted to ion fluxes, microvesicle formation and IL-6 release. J Cell Sci 112:297–305PubMedGoogle Scholar
  80. 80.
    Stanich JE, Gibbons SJ, Eisenman ST, Bardsley MR, Rock JR, Harfe BD, Ordog T, Farrugia G (2011) ANO1 as a regulator of proliferation. Am J Physiol 301:G1044–G1051Google Scholar
  81. 81.
    Suadicani SO, Brosnan CF, Scemes E (2006) P2X7 receptors mediate ATP release and amplification of astrocytic intercellular Ca2+ signaling. J Neurosci 26:1378–1385PubMedCentralCrossRefPubMedGoogle Scholar
  82. 82.
    Suzuki J, Umeda M, Sims PJ, Nagata S (2010) Calcium-dependent phospholipid scrambling by TMEM16F. Nature 468:834–838CrossRefPubMedGoogle Scholar
  83. 83.
    Takahashi T, Neher E, Sakmann B (1987) Rat brain serotonin receptors in Xenopus oocytes are coupled by intracellular calcium to endogenous channels. Proc Natl Acad Sci U S A 84:5063–5067PubMedCentralCrossRefPubMedGoogle Scholar
  84. 84.
    Tian Y, Schreiber R, Kunzelmann K (2012) Anoctamins are a family of Ca2+-activated Cl channels. J Cell Sci 125:4991–4998CrossRefPubMedGoogle Scholar
  85. 85.
    Tien J, Lee HY, Minor DL Jr, Jan YN, Jan LY (2013) Identification of a dimerization domain in the TMEM16A calcium-activated chloride channel (CaCC). Proc Natl Acad Sci U S A 110:6352–6357PubMedCentralCrossRefPubMedGoogle Scholar
  86. 86.
    Tokuyama Y, Hara M, Jones EM, Fan Z, Bell GI (1995) Cloning of rat and mouse P2Y purinoceptors. Biochem Biophys Res Commun 211:211–218CrossRefPubMedGoogle Scholar
  87. 87.
    Valera S, Hussy N, Evans RJ, Adami N, North RA, Surprenant A, Buell G (1994) A new class of ligand-gated ion channel defined by P2x receptor for extracellular ATP. Nature 371:516–519CrossRefPubMedGoogle Scholar
  88. 88.
    von Kügelgen I (2006) Pharmacological profiles of cloned mammalian P2Y-receptor subtypes. Pharmacol Ther 110:415–432CrossRefGoogle Scholar
  89. 89.
    Wang J, Haanes KA, Novak I (2013) Purinergic regulation of CFTR and Ca2+-activated Cl channels and K+ channels in human pancreatic duct epithelium. Am J Physiol 304:C673–C684CrossRefGoogle Scholar
  90. 90.
    Weber W (1999) Ion currents of Xenopus laevis oocytes: state of the art. Biochim Biophys Acta 1421:213–233CrossRefPubMedGoogle Scholar
  91. 91.
    Weber WM (1999) Endogenous ion channels in oocytes of xenopus laevis: recent developments. J Membr Biol 170:1–12CrossRefPubMedGoogle Scholar
  92. 92.
    Wilson HL, Wilson SA, Surprenant A, North RA (2002) Epithelial membrane proteins induce membrane blebbing and interact with the P2X7 receptor C terminus. J Biol Chem 277:34017–34023CrossRefPubMedGoogle Scholar
  93. 93.
    Yang YD, Cho H, Koo JY, Tak MH, Cho Y, Shim WS, Park SP, Lee J, Lee B, Kim BM, Raouf R, Shin YK, Oh U (2008) TMEM16A confers receptor-activated calcium-dependent chloride conductance. Nature 455:1210–1215CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Michaela Stolz
    • 1
  • Manuela Klapperstück
    • 2
  • Thomas Kendzierski
    • 2
  • Silvia Detro-dassen
    • 1
  • Anna Panning
    • 1
  • Günther Schmalzing
    • 1
  • Fritz Markwardt
    • 2
    Email author
  1. 1.Molecular PharmacologyRWTH Aachen UniversityAachenGermany
  2. 2.Julius-Bernstein-Institute for PhysiologyMartin-Luther-University Halle-WittenbergHalle/SaaleGermany

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