Advertisement

Pflügers Archiv - European Journal of Physiology

, Volume 468, Issue 2, pp 305–319 | Cite as

Expression of calcium-activated chloride channels Ano1 and Ano2 in mouse taste cells

  • Alexander P. Cherkashin
  • Alisa S. Kolesnikova
  • Michail V. Tarasov
  • Roman A. Romanov
  • Olga A. Rogachevskaja
  • Marina F. Bystrova
  • Stanislav S. KolesnikovEmail author
Sensory physiology

Abstract

Specialized Ca2+-dependent ion channels ubiquitously couple intracellular Ca2+ signals to a change in cell polarization. The existing physiological evidence suggests that Ca2+-activated Cl channels (CaCCs) are functional in taste cells. Because Ano1 and Ano2 encode channel proteins that form CaCCs in a variety of cells, we analyzed their expression in mouse taste cells. Transcripts for Ano1 and Ano2 were detected in circumvallate (CV) papillae, and their expression in taste cells was confirmed using immunohistochemistry. When dialyzed with CsCl, taste cells of the type III exhibited no ion currents dependent on cytosolic Ca2+. Large Ca2+-gated currents mediated by TRPM5 were elicited in type II cells by Ca2+ uncaging. When TRPM5 was inhibited by triphenylphosphine oxide (TPPO), ionomycin stimulated a small but resolvable inward current that was eliminated by anion channel blockers, including T16Ainh-A01 (T16), a specific Ano1 antagonist. This suggests that CaCCs, including Ano1-like channels, are functional in type II cells. In type I cells, CaCCs were prominently active, blockable with the CaCC antagonist CaCCinh-A01 but insensitive to T16. By profiling Ano1 and Ano2 expressions in individual taste cells, we revealed Ano1 transcripts in type II cells only, while Ano2 transcripts were detected in both type I and type II cells. P2Y agonists stimulated Ca2+-gated Cl currents in type I cells. Thus, CaCCs, possibly formed by Ano2, serve as effectors downstream of P2Y receptors in type I cells. While the role for TRPM5 in taste transduction is well established, the physiological significance of expression of CaCCs in type II cells remains to be elucidated.

Keywords

Taste cells Ca2+-gated Cl channels Ano1 Ano2 Purinergic transduction 

Notes

Acknowledgments

We thank Heinz Breer and Peter Mombaerts for providing OMP-GFP mice. This work was supported by the Russian Foundation for Basic Research (grants 13-04-00913a, 13-04-40082H, and 14-04-91157a).

Supplementary material

424_2015_1751_MOESM1_ESM.pdf (687 kb)
ESM 1 (PDF 687 kb)

References

  1. 1.
    Amjad A, Hernandez-Clavijo A, Pifferi S et al (2015) Conditional knockout of TMEM16A/anoctamin1 abolishes the calcium-activated chloride current in mouse vomeronasal sensory neurons. J Gen Physiol 145:285–301PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Bader CR, Bertrand D, Schwartz EA (1982) Voltage-activated and calcium-activated currents studied in solitary rod inner segments from the salamander retina. J Physiol 331:253–284PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Bartel DL, Sullivan SL, Lavoie EG et al (2006) Nucleoside triphosphate diphosphohydrolase-2 is the ecto-ATPase of type I cells in taste buds. J Comp Neurol 497:1–12PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Baryshnikov SG, Rogachevskaja OA, Kolesnikov SS (2003) Calcium signaling mediated by P2Y receptors in mouse taste cells. J Neurophysiol 90:3283–3294PubMedCrossRefGoogle Scholar
  5. 5.
    Bertuccio CA, Devor DC (2015) Intermediate conductance, Ca2+-activated K+ channels: a novel target for chronic renal diseases. Front Biol 10:52–60CrossRefGoogle Scholar
  6. 6.
    Billig GM, Pal B, Fidzinski P et al (2011) Ca2+-activated Cl currents are dispensable for olfaction. Nat Neurosci 14:763–769PubMedCrossRefGoogle Scholar
  7. 7.
    Burnstock G (2012) Purinergic signalling: its unpopular beginning, its acceptance and its exciting future. Bioessays 34:218–225PubMedCrossRefGoogle Scholar
  8. 8.
    Bystrova MF, Romanov RA, Rogachevskaya OA et al (2010) Functional expression of the extracellular calcium-sensing receptor in mouse taste cells. J Cell Sci 123:972–982PubMedCrossRefGoogle Scholar
  9. 9.
    Bystrova MF, Yatzenko YE, Fedorov IV et al (2006) P2Y isoforms operative in mouse taste cells. Cell Tissue Res 323:377–382PubMedCrossRefGoogle Scholar
  10. 10.
    Caputo A, Caci E, Ferrera L et al (2008) TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity. Science 322:590–594PubMedCrossRefGoogle Scholar
  11. 11.
    Chaudhari N (2014) Synaptic communication and signal processing among sensory cells in taste buds. J Physiol 592:3387–3392PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Chaudhari N, Roper SD (2010) The cell biology of taste. J Cell Biol 190:285–96PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Chen TY (2005) Structure and function of ClC channels. Annu Rev Physiol 67:809–839PubMedCrossRefGoogle Scholar
  14. 14.
    Chen Y, Sun XD, Herness S (1996) Characteristics of action potentials and their underlying outward currents in rat taste receptor cells. J Neurophysiol 75:820–831PubMedGoogle Scholar
  15. 15.
    Clapp TR, Medler KF, Damak S et al (2006) Mouse taste cells with G protein-coupled taste receptors lack voltage-gated calcium channels and SNAP-25. BMC Biol 4:7PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Clapp TR, Stone LM, Margolskee RF et al (2001) Immunocytochemical evidence for co-expression of type III IP3 receptor with signaling components of bitter taste transduction. BMC Neurosci 2:6PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Cummings TA, Powell J, Kinnamon SC (1993) Sweet taste transduction in hamster taste cells: evidence for the role of cyclic nucleotides. J Neurophysiol 70:2326–2336PubMedGoogle Scholar
  18. 18.
    Damak S, Rong M, Yasumatsu K et al (2006) TRPM5 null mice respond to bitter, sweet, and umami compounds. Chem Senses 31:253–264PubMedCrossRefGoogle Scholar
  19. 19.
    Dauner K, Lissmann J, Jeridi S et al (2012) Expression patterns of anoctamin 1 and anoctamin 2 chloride channels in the mammalian nose. Cell Tissue Res 347:327–341PubMedCrossRefGoogle Scholar
  20. 20.
    De La Fuente R, Namkung W, Mills A et al (2008) Small-molecule screen identifies inhibitors of a human intestinal calcium-activated chloride channel. Mol Pharmacol 73:758–68CrossRefGoogle Scholar
  21. 21.
    Duran C, Thompson CH, Xiao Q et al (2010) Chloride channels: often enigmatic, rarely predictable. Annu Rev Physiol 72:95–121PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Finger TE, Danilova V, Barrows J et al (2005) ATP signaling is crucial for communication from taste buds to gustatory nerves. Science 310:1495–1499PubMedCrossRefGoogle Scholar
  23. 23.
    Galindo BE, Vacquier VD (2005) Phylogeny of the TMEM16 protein family: some members are overexpressed in cancer. Int J Mol Med 16:919–924PubMedGoogle Scholar
  24. 24.
    Guinamard R, Salle L, Simard C (2011) The non-selective monovalent cationic channels TRPM4 and TRPM5. In: Islam MS (ed) Transient receptor potential channels. Springer, Netherlands, pp 147–171CrossRefGoogle Scholar
  25. 25.
    Hartzell C, Putzier I, Arreola J (2005) Calcium-activated chloride channels. Annu Rev Physiol 67:719–758PubMedCrossRefGoogle Scholar
  26. 26.
    Hartzell HC, Yu K, Xiao Q et al (2009) Anoctamin/TMEM16 family members are Ca2+-activated Cl channels. J Physiol 587:2127–2139PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Hayato R, Ohtubo Y, Yoshii K (2007) Functional expression of ionotropic purinergic receptors on mouse taste bud cells. J Physiol 584:473–488PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Hengl T, Kaneko H, Dauner K et al (2010) Molecular components of signal amplification in olfactory sensory cilia. Proc Natl Acad Sci U S A 107:6052–6057PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Huang YA, Dando R, Roper SD (2009) Autocrine and paracrine roles for ATP and serotonin in mouse taste buds. J Neurosci 29:13909–13918PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Huang YA, Stone LM, Pereira E et al (2011) Knocking out P2X receptors reduces transmitter secretion in taste buds. J Neurosci 31:13654–13661PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Huang F, Wong X, Jan LY (2012) International Union of Basic and Clinical Pharmacology. LXXXV: calcium-activated chloride channels. Pharmacol Rev 64:1–15PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Jentsch TJ, Stein V, Weinreich F et al (2002) Molecular structure and physiological function of chloride channels. Physiol Rev 82:503–568PubMedCrossRefGoogle Scholar
  33. 33.
    Kataoka S, Toyono T, Seta Y et al (2004) Expression of P2Y1 receptors in rat taste buds. Histochem Cell Biol 121:419–426PubMedCrossRefGoogle Scholar
  34. 34.
    Kataoka S, Yang R, Ishimaru Y et al (2008) The candidate sour taste receptor, PKD2L1, is expressed by type III taste cells in the mouse. Chem Senses 33:243–254PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Kim YV, Bobkov YV, Kolesnikov SS (2000) Adenosine trisphosphate mobilizes cytosolic calcium and modulates ionic currents in mouse taste receptor cells. Neurosci Lett 290:165–168PubMedCrossRefGoogle Scholar
  36. 36.
    Kim S, Ma L, Yu CR (2011) Requirement of calcium-activated chloride channels in the activation of mouse vomeronasal neurons. Nat Commun 2:365PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Kinnamon S (2013) Neurosensory transmission without a synapse: new perspectives on taste signaling. BMC Biol 11:42PubMedPubMedCentralGoogle Scholar
  38. 38.
    Kleene SJ, Gesteland RC (1991) Calcium-activated chloride conductance in frog olfactory cilia. J Neurosci 11:3624–3629PubMedGoogle Scholar
  39. 39.
    Kolesnikov SS, Margolskee RF (1998) Extracellular K+ activates a K+- and H+-permeable conductance in frog taste cells. J Physiol 507:415–432PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Kunzelmann K, Schreiber R, Kmit A et al (2012) Expression and function of epithelial anoctamins. Exp Physiol 97:184–192PubMedCrossRefGoogle Scholar
  41. 41.
    Kurahashi T, Yau KW (1993) Co-existence of cationic and chloride components in odorant-induced current of vertebrate olfactory receptor cells. Nature 363:71–74PubMedCrossRefGoogle Scholar
  42. 42.
    Liman ER (2010) Changing taste by targeting the ion channel TRPM5. Open Drug Discov J 2:98–102CrossRefGoogle Scholar
  43. 43.
    Liu Y, Zhang H, Huang D et al (2015) Characterization of the effects of Cl channel modulators on TMEM16A and bestrophin-1 Ca2+ activated Cl channels. Pflüg Arch 467:1417–1430CrossRefGoogle Scholar
  44. 44.
    Lowe G, Gold GH (1993) Nonlinear amplification by calcium-dependent chloride channels in olfactory receptor cells. Nature 366:283–286PubMedCrossRefGoogle Scholar
  45. 45.
    Ma Z, Siebert AP, Cheung KH et al (2012) Calcium homeostasis modulator 1 (CALHM1) is the pore-forming subunit of an ion channel that mediates extracellular Ca2+ regulation of neuronal excitability. Proc Natl Acad Sci U S A 109:E1963–E1971PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Maricq AV, Korenbrot JI (1988) Calcium and calcium-dependent chloride currents generate action potentials in solitary cone photoreceptors. Neuron 1:503–515PubMedCrossRefGoogle Scholar
  47. 47.
    Maurya DK, Menini A (2014) Developmental expression of the calcium-activated chloride channels TMEM16A and TMEM16B in the mouse olfactory epithelium. Dev Neurobiol 74:657–675PubMedCrossRefGoogle Scholar
  48. 48.
    McBride DW Jr, Roper SD (1991) Ca2+-dependent chloride conductance in Necturus taste cells. J Membr Biol 124:85–93PubMedCrossRefGoogle Scholar
  49. 49.
    Medler KF, Margolslee RF, Kinnamon SC (2003) Electrophysiological characterization of voltage-gated currents in defined taste cell types in mice. J Neurosci 23:2608–261PubMedGoogle Scholar
  50. 50.
    Moyer BD, Hevezi P, Gao N et al (2009) Expression of genes encoding multi-transmembrane proteins in specific primate taste cell populations. PLoS One 4:e7682PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Namkung W, Phuan PW, Verkman AS (2010) TMEM16A inhibitors reveal TMEM16A as a minor component of calcium-activated chloride channel conductance in airway and intestinal epithelial cells. J Biol Chem 286:2365–2374PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Palmer RK, Atwal K, Bakaj I et al (2010) Triphenylphosphine oxide is a potent and selective inhibitor of the transient receptor potential melastatin-5 ion channel. Assay Drug Dev Technol 8:703–713PubMedCrossRefGoogle Scholar
  53. 53.
    Pedemonte N, Galietta LJV (2014) Structure and function of TMEM16 proteins (anoctamins). Physiol Rev 94:419–459PubMedCrossRefGoogle Scholar
  54. 54.
    Perez CA, Huang L, Rong M et al (2002) A transient receptor potential channel expressed in taste receptor cells. Nat Neurosci 5:1169–1176PubMedCrossRefGoogle Scholar
  55. 55.
    Pifferi S, Dibattista M, Menini A (2009) TMEM16B induces chloride currents activated by calcium in mammalian cells. Pflugers Arch 458:1023–1038PubMedCrossRefGoogle Scholar
  56. 56.
    Rasche S, Toetter B, Adler J et al (2010) TMEM16b is specifically expressed in the cilia of olfactory sensory neurons. Chem Senses 35:239–245PubMedCrossRefGoogle Scholar
  57. 57.
    Romanov RA, Kolesnikov SS (2006) Electrophysiologically identified subpopulations of taste bud cells. Neurosci Lett 395:249–254PubMedCrossRefGoogle Scholar
  58. 58.
    Romanov RA, Rogachevskaja OA, Bystrova MF et al (2007) Afferent neurotransmission mediated by hemichannels in mammalian taste cells. EMBO J 26:657–667PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Romanov RA, Rogachevskaja OA, Bystrova MF et al (2012) Electrical excitability of taste cells. Mechanisms and possible physiological significance. Biochem (Mosc) Suppl Series A: Membrane Cell Biol 6:169–185CrossRefGoogle Scholar
  60. 60.
    Sagheddu C, Boccaccio A, Dibattista M et al (2010) Calcium concentration jumps reveal dynamic ion selectivity of calcium-activated chloride currents in mouse olfactory sensory neurons and TMEM16b-transfected HEK 293T cells. J Physiol 588:4189–4204PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Sauter DRP, Novak I, Pedersen SF et al (2015) Ano1 (TMEM16A) in pancreatic ductal adenocarcinoma (PDAC). Pflugers Arch 467:1495–1508PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Schroeder BC, Cheng T, Jan YN et al (2008) Expression cloning of TMEM16A as a calcium-activated chloride channel subunit. Cell 134:1019–1029PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Scudieri P, Sondo E, Ferrera L et al (2012) The anoctamin family: TMEM16A and TMEM16B as calcium-activated chloride channels. Exp Physiol 97:177–183PubMedCrossRefGoogle Scholar
  64. 64.
    Stephan AB, Shum EY, Hirsh S et al (2009) Ano2 is the cilial calcium-activated chloride channel that may mediate olfactory amplification. Proc Natl Acad Sci U S A 106:11776–11781PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Stocker M (2004) Ca2+-activated K+ channels: molecular determinants and function of the SK family. Nat Rev Neurosci 5:758–770PubMedCrossRefGoogle Scholar
  66. 66.
    Stohr H, Heisig JB, Benz PM et al (2009) TMEM16B, a novel protein with calcium-dependent chloride channel activity, associates with a presynaptic protein complex in photoreceptor terminals. J Neurosci 29:6809–6818PubMedCrossRefGoogle Scholar
  67. 67.
    Suzuki M, Morita T, Iwamoto T (2006) Diversity of Cl channels. Cell Mol Life Sci 63:12–24PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Taruno A, Vingtdeux V, Ohmoto M et al (2013) CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes. Nature 495:223–226PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Toro L, Li M, Zhang Z et al (2014) MaxiK channel and cell signaling. Pflugers Arch 466:875–886PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    von Kugelgen I (2006) Pharmacological profiles of cloned mammalian P2Y-receptor subtypes. Pharmacol Therap 110:415–432CrossRefGoogle Scholar
  71. 71.
    Wladkowski SL, Lin W, McPheeters M et al (1998) A basolateral chloride conductance in rat lingual epithelium. J Membr Biol 164:91–101PubMedCrossRefGoogle Scholar
  72. 72.
    Xiao Q, Yu K, Perez-Cornejo P et al (2011) Voltage- and calcium-dependent gating of TMEM16A/Ano1 chloride channels are physically coupled by the first intracellular loop. Proc Natl Acad Sci U S A 108:8891–8896PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Yang YD, Cho H, Koo JY et al (2008) TMEM16A confers receptor-activated calcium dependent chloride conductance. Nature 455:1210–1215PubMedCrossRefGoogle Scholar
  74. 74.
    Yang C, Delay RJ (2010) Calcium-activated chloride current amplifies the response to urine in mouse vomeronasal sensory neurons. J Gen Physiol 135:3–13PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Yu T, McIntyre JC, Bose SC et al (2005) Differentially expressed transcripts from phenotypically identified olfactory sensory neurons. J Comp Neurol 483:251–262PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Zhang Y, Hoon MA, Chandrashekar J et al (2003) Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell 112:293–301PubMedCrossRefGoogle Scholar
  77. 77.
    Zhang Z, Zhao Z, Margolskee R et al (2007) The transduction channel TRPM5 is gated by intracellular calcium in taste cells. J Neurosci 27:5777–5786PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Alexander P. Cherkashin
    • 1
  • Alisa S. Kolesnikova
    • 1
  • Michail V. Tarasov
    • 1
  • Roman A. Romanov
    • 2
  • Olga A. Rogachevskaja
    • 1
  • Marina F. Bystrova
    • 1
  • Stanislav S. Kolesnikov
    • 1
    Email author
  1. 1.Institute of Cell BiophysicsRussian Academy of SciencesPushchinoRussia
  2. 2.Department of Molecular Neurosciences, Center for Brain ResearchMedical University of ViennaViennaAustria

Personalised recommendations