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.
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References
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 145:285–301
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 331:253–284
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 497:1–12
Baryshnikov SG, Rogachevskaja OA, Kolesnikov SS (2003) Calcium signaling mediated by P2Y receptors in mouse taste cells. J Neurophysiol 90:3283–3294
Bertuccio CA, Devor DC (2015) Intermediate conductance, Ca2+-activated K+ channels: a novel target for chronic renal diseases. Front Biol 10:52–60
Billig GM, Pal B, Fidzinski P et al (2011) Ca2+-activated Cl− currents are dispensable for olfaction. Nat Neurosci 14:763–769
Burnstock G (2012) Purinergic signalling: its unpopular beginning, its acceptance and its exciting future. Bioessays 34:218–225
Bystrova MF, Romanov RA, Rogachevskaya OA et al (2010) Functional expression of the extracellular calcium-sensing receptor in mouse taste cells. J Cell Sci 123:972–982
Bystrova MF, Yatzenko YE, Fedorov IV et al (2006) P2Y isoforms operative in mouse taste cells. Cell Tissue Res 323:377–382
Caputo A, Caci E, Ferrera L et al (2008) TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity. Science 322:590–594
Chaudhari N (2014) Synaptic communication and signal processing among sensory cells in taste buds. J Physiol 592:3387–3392
Chaudhari N, Roper SD (2010) The cell biology of taste. J Cell Biol 190:285–96
Chen TY (2005) Structure and function of ClC channels. Annu Rev Physiol 67:809–839
Chen Y, Sun XD, Herness S (1996) Characteristics of action potentials and their underlying outward currents in rat taste receptor cells. J Neurophysiol 75:820–831
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 4:7
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 2:6
Cummings TA, Powell J, Kinnamon SC (1993) Sweet taste transduction in hamster taste cells: evidence for the role of cyclic nucleotides. J Neurophysiol 70:2326–2336
Damak S, Rong M, Yasumatsu K et al (2006) TRPM5 null mice respond to bitter, sweet, and umami compounds. Chem Senses 31:253–264
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 347:327–341
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 73:758–68
Duran C, Thompson CH, Xiao Q et al (2010) Chloride channels: often enigmatic, rarely predictable. Annu Rev Physiol 72:95–121
Finger TE, Danilova V, Barrows J et al (2005) ATP signaling is crucial for communication from taste buds to gustatory nerves. Science 310:1495–1499
Galindo BE, Vacquier VD (2005) Phylogeny of the TMEM16 protein family: some members are overexpressed in cancer. Int J Mol Med 16:919–924
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 147–171
Hartzell C, Putzier I, Arreola J (2005) Calcium-activated chloride channels. Annu Rev Physiol 67:719–758
Hartzell HC, Yu K, Xiao Q et al (2009) Anoctamin/TMEM16 family members are Ca2+-activated Cl− channels. J Physiol 587:2127–2139
Hayato R, Ohtubo Y, Yoshii K (2007) Functional expression of ionotropic purinergic receptors on mouse taste bud cells. J Physiol 584:473–488
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 107:6052–6057
Huang YA, Dando R, Roper SD (2009) Autocrine and paracrine roles for ATP and serotonin in mouse taste buds. J Neurosci 29:13909–13918
Huang YA, Stone LM, Pereira E et al (2011) Knocking out P2X receptors reduces transmitter secretion in taste buds. J Neurosci 31:13654–13661
Huang F, Wong X, Jan LY (2012) International Union of Basic and Clinical Pharmacology. LXXXV: calcium-activated chloride channels. Pharmacol Rev 64:1–15
Jentsch TJ, Stein V, Weinreich F et al (2002) Molecular structure and physiological function of chloride channels. Physiol Rev 82:503–568
Kataoka S, Toyono T, Seta Y et al (2004) Expression of P2Y1 receptors in rat taste buds. Histochem Cell Biol 121:419–426
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 33:243–254
Kim YV, Bobkov YV, Kolesnikov SS (2000) Adenosine trisphosphate mobilizes cytosolic calcium and modulates ionic currents in mouse taste receptor cells. Neurosci Lett 290:165–168
Kim S, Ma L, Yu CR (2011) Requirement of calcium-activated chloride channels in the activation of mouse vomeronasal neurons. Nat Commun 2:365
Kinnamon S (2013) Neurosensory transmission without a synapse: new perspectives on taste signaling. BMC Biol 11:42
Kleene SJ, Gesteland RC (1991) Calcium-activated chloride conductance in frog olfactory cilia. J Neurosci 11:3624–3629
Kolesnikov SS, Margolskee RF (1998) Extracellular K+ activates a K+- and H+-permeable conductance in frog taste cells. J Physiol 507:415–432
Kunzelmann K, Schreiber R, Kmit A et al (2012) Expression and function of epithelial anoctamins. Exp Physiol 97:184–192
Kurahashi T, Yau KW (1993) Co-existence of cationic and chloride components in odorant-induced current of vertebrate olfactory receptor cells. Nature 363:71–74
Liman ER (2010) Changing taste by targeting the ion channel TRPM5. Open Drug Discov J 2:98–102
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 467:1417–1430
Lowe G, Gold GH (1993) Nonlinear amplification by calcium-dependent chloride channels in olfactory receptor cells. Nature 366:283–286
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–E1971
Maricq AV, Korenbrot JI (1988) Calcium and calcium-dependent chloride currents generate action potentials in solitary cone photoreceptors. Neuron 1:503–515
Maurya DK, Menini A (2014) Developmental expression of the calcium-activated chloride channels TMEM16A and TMEM16B in the mouse olfactory epithelium. Dev Neurobiol 74:657–675
McBride DW Jr, Roper SD (1991) Ca2+-dependent chloride conductance in Necturus taste cells. J Membr Biol 124:85–93
Medler KF, Margolslee RF, Kinnamon SC (2003) Electrophysiological characterization of voltage-gated currents in defined taste cell types in mice. J Neurosci 23:2608–261
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:e7682
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 286:2365–2374
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 8:703–713
Pedemonte N, Galietta LJV (2014) Structure and function of TMEM16 proteins (anoctamins). Physiol Rev 94:419–459
Perez CA, Huang L, Rong M et al (2002) A transient receptor potential channel expressed in taste receptor cells. Nat Neurosci 5:1169–1176
Pifferi S, Dibattista M, Menini A (2009) TMEM16B induces chloride currents activated by calcium in mammalian cells. Pflugers Arch 458:1023–1038
Rasche S, Toetter B, Adler J et al (2010) TMEM16b is specifically expressed in the cilia of olfactory sensory neurons. Chem Senses 35:239–245
Romanov RA, Kolesnikov SS (2006) Electrophysiologically identified subpopulations of taste bud cells. Neurosci Lett 395:249–254
Romanov RA, Rogachevskaja OA, Bystrova MF et al (2007) Afferent neurotransmission mediated by hemichannels in mammalian taste cells. EMBO J 26:657–667
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 6:169–185
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 588:4189–4204
Sauter DRP, Novak I, Pedersen SF et al (2015) Ano1 (TMEM16A) in pancreatic ductal adenocarcinoma (PDAC). Pflugers Arch 467:1495–1508
Schroeder BC, Cheng T, Jan YN et al (2008) Expression cloning of TMEM16A as a calcium-activated chloride channel subunit. Cell 134:1019–1029
Scudieri P, Sondo E, Ferrera L et al (2012) The anoctamin family: TMEM16A and TMEM16B as calcium-activated chloride channels. Exp Physiol 97:177–183
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 106:11776–11781
Stocker M (2004) Ca2+-activated K+ channels: molecular determinants and function of the SK family. Nat Rev Neurosci 5:758–770
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 29:6809–6818
Suzuki M, Morita T, Iwamoto T (2006) Diversity of Cl− channels. Cell Mol Life Sci 63:12–24
Taruno A, Vingtdeux V, Ohmoto M et al (2013) CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes. Nature 495:223–226
Toro L, Li M, Zhang Z et al (2014) MaxiK channel and cell signaling. Pflugers Arch 466:875–886
von Kugelgen I (2006) Pharmacological profiles of cloned mammalian P2Y-receptor subtypes. Pharmacol Therap 110:415–432
Wladkowski SL, Lin W, McPheeters M et al (1998) A basolateral chloride conductance in rat lingual epithelium. J Membr Biol 164:91–101
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 108:8891–8896
Yang YD, Cho H, Koo JY et al (2008) TMEM16A confers receptor-activated calcium dependent chloride conductance. Nature 455:1210–1215
Yang C, Delay RJ (2010) Calcium-activated chloride current amplifies the response to urine in mouse vomeronasal sensory neurons. J Gen Physiol 135:3–13
Yu T, McIntyre JC, Bose SC et al (2005) Differentially expressed transcripts from phenotypically identified olfactory sensory neurons. J Comp Neurol 483:251–262
Zhang Y, Hoon MA, Chandrashekar J et al (2003) Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell 112:293–301
Zhang Z, Zhao Z, Margolskee R et al (2007) The transduction channel TRPM5 is gated by intracellular calcium in taste cells. J Neurosci 27:5777–5786
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).
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Alexander P. Cherkashin and Alisa S. Kolesnikova contributed equally to this work.
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Cherkashin, A.P., Kolesnikova, A.S., Tarasov, M.V. et al. Expression of calcium-activated chloride channels Ano1 and Ano2 in mouse taste cells. Pflugers Arch - Eur J Physiol 468, 305–319 (2016). https://doi.org/10.1007/s00424-015-1751-z
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DOI: https://doi.org/10.1007/s00424-015-1751-z