The long tale of the calcium activated Cl− channels in olfactory transduction

Channels

Volumn 11, Issue 5, 2017, Pages 399-414

  Dibattista, Michele ^a   Pifferi, Simone ^b   Boccaccio, Anna ^c   Menini, Anna ^b   Reisert, Johannes ^d  

^a UNIVERSITY OF BARI   (Italy)

^b SISSA   (Italy)

^c CNR   (Italy)

^d MONELL CHEMICAL SENSES CENTER   (United States)

Author keywords

calcium activated chloride channels; electrophysiology; olfactory behavior; olfactory transduction; TMEM16B

Indexed keywords

CALCIUM ACTIVATED CHLORIDE CHANNEL; CYCLIC AMP; CYCLIC NUCLEOTIDE GATED CHANNEL; NEUROPILIN 1; PROTEIN; SODIUM POTASSIUM CHLORIDE COTRANSPORTER 1; TMEM 16B PROTEIN; UNCLASSIFIED DRUG; ANO2 PROTEIN, MOUSE; ANOCTAMIN; CALCIUM;

ACTION POTENTIAL; BIOPHYSICS; CILIUM; ELECTRIC ACTIVITY; ELECTROPHYSIOLOGY; FIRING RATE; GENE INACTIVATION; GLOMERULUS; HEK293 CELL LINE; HUMAN; NONHUMAN; OLFACTOMETRY; OLFACTORY BULB; OLFACTORY EPITHELIUM; OLFACTORY RECEPTOR; OLFACTORY RECEPTOR NEURON; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; SMELLING; ANIMAL; GENETICS; KNOCKOUT MOUSE; METABOLISM; ODOR;

ANIMALS; ANOCTAMINS; CALCIUM; HUMANS; MICE, KNOCKOUT; OLFACTORY RECEPTOR NEURONS; SMELL;

EID: 85018664845     PISSN: 19336950     EISSN: 19336969     Source Type: Journal    
DOI: 10.1080/19336950.2017.1307489     Document Type: Review

References (110)

1. Axel R., Buck L. A novel multigene family may encode odorant receptors: A molecular basis for odor recognition. Cell 1991; 65:175-87; PMID:1840504; http://dx.doi.org/10.1016/0092-8674(91)90418-X
2. Kleene SJ, Gesteland RC. Calcium-activated chloride conductance in frog olfactory cilia. J Neurosci 1991; 11:3624-9; PMID:1941099
3. Kurahashi T, Yau KW. Co-existence of cationic and chloride components in odorant-induced current of vertebrate olfactory receptor cells. Nature 1993; 363:71-4; PMID:7683113; http://dx.doi.org/10.1038/363071a0
4. Zhainazarov AB, Ache BW. Odor-induced currents in Xenopus olfactory receptor cells measured with perforated-patch recording. J Neurophysiol 1995; 74:479-83; PMID:7472351
5. Reisert J, Bauer PJ, Yau KW, Frings S. The Ca-activated Cl channel and its control in rat olfactory receptor neurons. J Gen Physiol 2003; 122:349-63; PMID:12939394; http://dx.doi.org/10.1085/jgp.200308888
6. Sato K, Suzuki N. The contribution of a Ca(2+)-activated Cl(−) conductance to amino-acid-induced inward current responses of ciliated olfactory neurons of the rainbow trout. J Exp Biol 2000; 203:253-62; PMID:10607535
7. Caputo A, Caci E, Ferrera L, Pedemonte N, Barsanti C, Sondo E, Pfeffer U, Ravazzolo R, Zegarra-Moran O, Galietta LJ. TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity. Science 2008; 322:590-4; PMID:18772398; http://dx.doi.org/10.1126/science.1163518
8. Schroeder BC, Cheng T, Jan YN, Jan LY. Expression cloning of TMEM16A as a calcium-activated chloride channel subunit. Cell 2008; 134:1019-29; PMID:18805094; http://dx.doi.org/10.1016/j.cell.2008.09.003
9. Yang YD, Cho H, Koo JY, Tak MH, Cho Y, Shim WS, Park SP, Lee J, Lee B, Kim BM, et al. TMEM16A confers receptor-activated calcium-dependent chloride conductance. Nature 2008; 455:1210-5; PMID:18724360; http://dx.doi.org/10.1038/nature07313
10. Malnic B, Hirono J, Sato T, Buck LB. Combinatorial receptor codes for odors. Cell 1999; 96:713-23; PMID:10089886; http://dx.doi.org/10.1016/S0092-8674(00)80581-4
11. Jones DT, Reed RR. Golf: an olfactory neuron specific-G protein involved in odorant signal transduction. Science 1989; 244:790-5; PMID:2499043; http://dx.doi.org/10.1126/science.2499043
12. Bakalyar HA, Reed RR. Identification of a specialized adenylyl cyclase that may mediate odorant detection. Science 1990; 250:1403-6; PMID:2255909; http://dx.doi.org/10.1126/science.2255909
13. Nakamura T, Gold GH. A cyclic nucleotide-gated conductance in olfactory receptor cilia. Nature 1987; 325:442-4; PMID:3027574; http://dx.doi.org/10.1038/325442a0
14. Firestein S, Zufall F, Shepherd GM. Single odor-sensitive channels in olfactory receptor neurons are also gated by cyclic nucleotides. J Neurosci 1991; 11:3565-72; PMID:1719165
15. Kaneko H, Putzier I, Frings S, Kaupp UB, Gensch T. Chloride accumulation in mammalian olfactory sensory neurons. J Neurosci 2004; 24:7931-8; PMID:15356206; http://dx.doi.org/10.1523/JNEUROSCI.2115-04.2004
16. Reuter D, Zierold K, Schröder WH, Frings S. A depolarizing chloride current contributes to chemoelectrical transduction in olfactory sensory neurons in Situ. J Neurosci 1998; 18:6623-30; PMID:9712634
17. Reisert J, Lai J, Yau KW, Bradley J. Mechanism of the excitatory Cl− response in mouse olfactory receptor neurons. Neuron 2005; 45:553-61; PMID:15721241; http://dx.doi.org/10.1016/j.neuron.2005.01.012
18. Lowe G, Gold GH. Nonlinear amplification by calcium-dependent chloride channels in olfactory receptor cells. Nature 1993; 366:283-6; PMID:8232590; http://dx.doi.org/10.1038/366283a0
19. Boccaccio A, Menini A. Temporal development of cyclic nucleotide-gated and Ca2+-activated Cl− currents in isolated mouse olfactory sensory neurons. J Neurophysiol 2007; 98:153-60; PMID:17460108; http://dx.doi.org/10.1152/jn.00270.2007
20. Cygnar KD, Zhao H. Phosphodiesterase 1C is dispensable for rapid response termination of olfactory sensory neurons. Nat Neurosci 2009; 12:454-62; PMID:19305400; http://dx.doi.org/10.1038/nn.2289
21. Boccaccio A, Lagostena L, Hagen V, Menini A. Fast Adaptation in Mouse Olfactory Sensory Neurons Does Not Require the Activity of Phosphodiesterase. J Gen Physiol 2006; 128:171-84; PMID:16880265; http://dx.doi.org/10.1085/jgp.200609555
22. Flannery RJ, French DA, Kleene SJ. Clustering of cyclic-nucleotide-gated channels in olfactory cilia. Biophys J 2006; 91:179-88; PMID:16603488; http://dx.doi.org/10.1529/biophysj.105.079046
23. Chen C, Nakamura T, Koutalos Y. Cyclic AMP diffusion coefficient in frog olfactory cilia. Biophys J 1999; 76:2861-7; PMID:10233102; http://dx.doi.org/10.1016/S0006-3495(99)77440-0
24. Reisert J, Matthews HR. Response properties of isolated mouse olfactory receptor cells. J Physiol 2001; 530:113-22; PMID:11136863; http://dx.doi.org/10.1111/j.1469-7793.2001.0113m.x
25. Antolin S, Matthews HR. The effect of external sodium concentration on sodium–calcium exchange in frog olfactory receptor cells. J Physiol 2007; 581:495-503; PMID:17379630; http://dx.doi.org/10.1113/jphysiol.2007.131094
26. Reisert J, Matthews HR. Na+-dependent Ca2+ Extrusion Governs Response Recovery in Frog Olfactory Receptor Cells. J Gen Physiol 1998; 112:529-35; PMID:9806962; http://dx.doi.org/10.1085/jgp.112.5.529
27. Pyrski M, Koo JH, Polumuri SK, Ruknudin AM, Margolis JW, Schulze DH, Margolis FL. Sodium/calcium exchanger expression in the mouse and rat olfactory systems. J Comp Neurol 2007; 501:944-58; PMID:17311327; http://dx.doi.org/10.1002/cne.21290
28. Stephan AB, Tobochnik S, Dibattista M, Wall CM, Reisert J, Zhao H. The Na(+)/Ca(2+) exchanger NCKX4 governs termination and adaptation of the mammalian olfactory response. Nat Neurosci 2012; 15:131-7; http://dx.doi.org/10.1038/nn.2943
29. Ferguson CH, Zhao H. Simultaneous Loss of NCKX4 and CNG Channel Desensitization Impairs Olfactory Sensitivity. J Neurosci Off J Soc Neurosci 2017; 37:110-9; http://dx.doi.org/10.1523/JNEUROSCI.2527-16.2017
30. Fluegge D, Moeller LM, Cichy A, Gorin M, Weth A, Veitinger S, Cainarca S, Lohmer S, Corazza S, Neuhaus EM, et al. Mitochondrial Ca(2+) mobilization is a key element in olfactory signaling. Nat Neurosci 2012; 15:754-62; PMID:22446879; http://dx.doi.org/10.1038/nn.3074
31. Bradley J, Li J, Davidson N, Lester HA, Zinn K. Heteromeric olfactory cyclic nucleotide-gated channels: a subunit that confers increased sensitivity to cAMP. Proc Natl Acad Sci U S A 1994; 91:8890-4; PMID:7522325; http://dx.doi.org/10.1073/pnas.91.19.8890
32. Liman ER, Buck LB. A second subunit of the olfactory cyclic nucleotide-gated channel confers high sensitivity to cAMP. Neuron 1994; 13:611-21; PMID:7522482; http://dx.doi.org/10.1016/0896-6273(94)90029-9
33. Sautter A, Zong X, Hofmann F, Biel M. An isoform of the rod photoreceptor cyclic nucleotide-gated channel beta subunit expressed in olfactory neurons. Proc Natl Acad Sci U S A 1998; 95:4696-701; PMID:9539801; http://dx.doi.org/10.1073/pnas.95.8.4696
34. Bönigk W, Bradley J, Müller F, Sesti F, Boekhoff I, Ronnett GV, Kaupp UB, Frings S. The native rat olfactory cyclic nucleotide-gated channel is composed of three distinct subunits. J Neurosci 1999; 19:5332-47; PMID:10377344
35. Zheng J, Zagotta WN. Stoichiometry and assembly of olfactory cyclic nucleotide-gated channels. Neuron 2004; 42:411-21; PMID:15134638; http://dx.doi.org/10.1016/S0896-6273(04)00253-3
36. Dhallan RS, Yau KW, Schrader KA, Reed RR. Primary structure and functional expression of a cyclic nucleotide-activated channel from olfactory neurons. Nature 1990; 347:184-7; PMID:1697649; http://dx.doi.org/10.1038/347184a0
37. Ludwig J, Margalit T, Eismann E, Lancet D, Kaupp UB. Primary structure of cAMP-gated channel from bovine olfactory epithelium. FEBS Lett 1990; 270:24-9; PMID:1699793; http://dx.doi.org/10.1016/0014-5793(90)81226-E
38. Frings S, Lynch JW, Lindemann B. Properties of cyclic nucleotide-gated channels mediating olfactory transduction. Activation, selectivity, and blockage. J Gen Physiol 1992; 100:45-67; http://dx.doi.org/10.1085/jgp.100.1.45
39. Kurahashi T, Kaneko A. Gating properties of the cAMP-gated channel in toad olfactory receptor cells. J Physiol 1993; 466:287-302; PMID:8410695
40. Nache V, Schulz E, Zimmer T, Kusch J, Biskup C, Koopmann R, Hagen V, Benndorf K. Activation of olfactory-type cyclic nucleotide-gated channels is highly cooperative. J Physiol 2005; 569:91-102; PMID:16081488; http://dx.doi.org/10.1113/jphysiol.2005.092304
41. Biskup C, Kusch J, Schulz E, Nache V, Schwede F, Lehmann F, Hagen V, Benndorf K. Relating ligand binding to activation gating in CNGA2 channels. Nature 2007; 446:440-3; PMID:17322905; http://dx.doi.org/10.1038/nature05596
42. Larsson HP, Kleene SJ, Lecar H. Noise analysis of ion channels in non-space-clamped cables: estimates of channel parameters in olfactory cilia. Biophys J 1997; 72:1193-203; PMID:9138566; http://dx.doi.org/10.1016/S0006-3495(97)78767-8
43. Kleene SJ. High-gain, low-noise amplification in olfactory transduction. Biophys J 1997; 73:1110-7; PMID:9251827; http://dx.doi.org/10.1016/S0006-3495(97)78143-8
44. Kramer RH, Siegelbaum SA. Intracellular Ca2+ regulates the sensitivity of cyclic nucleotide-gated channels in olfactory receptor neurons. Neuron 1992; 9:897-906; PMID:1384576; http://dx.doi.org/10.1016/0896-6273(92)90242-6
45. Zufall F, Firestein S, Shepherd GM. Analysis of single cyclic nucleotide-gated channels in olfactory receptor cells. J Neurosci 1991; 11:3573-80; PMID:1719166
46. Dzeja C, Hagen V, Kaupp UB, Frings S. Ca2+ permeation in cyclic nucleotide-gated channels. EMBO J 1999; 18:131-44; PMID:9878057; http://dx.doi.org/10.1093/emboj/18.1.131
47. Pifferi S, Boccaccio A, Menini A. Cyclic nucleotide-gated ion channels in sensory transduction. FEBS Lett 2006; 580:2853-9; PMID:16631748; http://dx.doi.org/10.1016/j.febslet.2006.03.086
48. Reisert J, Zhao H. Response kinetics of olfactory receptor neurons and the implications in olfactory coding. J Gen Physiol 2011; 138:303-10; PMID:21875979; http://dx.doi.org/10.1085/jgp.201110645
49. Song Y, Cygnar KD, Sagdullaev B, Valley M, Hirsh S, Stephan A, Reisert J, Zhao H. Olfactory CNG channel desensitization by Ca2+/CaM via the B1b subunit affects response termination but not sensitivity to recurring stimulation. Neuron 2008; 58:374-86; PMID:18466748; http://dx.doi.org/10.1016/j.neuron.2008.02.029
50. Menini A. Calcium signalling and regulation in olfactory neurons. Curr Opin Neurobiol 1999; 9:419-26; PMID:10448159; http://dx.doi.org/10.1016/S0959-4388(99)80063-4
51. Kurahashi T, Menini A. Mechanism of odorant adaptation in the olfactory receptor cell. Nature 1997; 385:725-9; PMID:9034189; http://dx.doi.org/10.1038/385725a0
52. De Palo G, Boccaccio A, Miri A, Menini A, Altafini C. A dynamical feedback model for adaptation in the olfactory transduction pathway. Biophys J 2012; 102:2677-86; PMID:22735517; http://dx.doi.org/10.1016/j.bpj.2012.04.040
53. Cygnar KD, Stephan AB, Zhao H. Analyzing responses of mouse olfactory sensory neurons using the air-phase electroolfactogram recording. J Vis Exp JoVE 2010; (37) pii: 1850; PMID:20197755
54. Pinato G, Rievaj J, Pifferi S, Dibattista M, Masten L, Menini A. Electroolfactogram responses from organotypic cultures of the olfactory epithelium from postnatal mice. Chem Senses 2008; 33:397-404; PMID:18303030; http://dx.doi.org/10.1093/chemse/bjn007
55. Brunet LJ, Gold GH, Ngai J. General anosmia caused by a targeted disruption of the mouse olfactory cyclic nucleotide–gated cation channel. Neuron 1996; 17:681-93; PMID:8893025; http://dx.doi.org/10.1016/S0896-6273(00)80200-7
56. Zhao H, Reed RR. X Inactivation of the OCNC1 channel gene reveals a role for activity-dependent competition in the olfactory system. Cell 2001; 104:651-60; PMID:11257220; http://dx.doi.org/10.1016/S0092-8674(01)00262-8
57. Lin W, Arellano J, Slotnick B, Restrepo D. Odors detected by mice deficient in cyclic nucleotide-gated channel subunit A2 stimulate the main olfactory system. J Neurosci 2004; 24:3703-10; PMID:15071119; http://dx.doi.org/10.1523/JNEUROSCI.0188-04.2004
58. Boccaccio A, Sagheddu C, Menini A. Flash photolysis of caged compounds in the cilia of olfactory sensory neurons. J Vis Exp JoVE 2011; e3195; PMID:22064384
59. Pifferi S, Pascarella G, Boccaccio A, Mazzatenta A, Gustincich S, Menini A, Zucchelli S. Bestrophin-2 is a candidate calcium-activated chloride channel involved in olfactory transduction. Proc Natl Acad Sci 2006; 103:12929-34; PMID:16912113; http://dx.doi.org/10.1073/pnas.0604505103
60. Sagheddu C, Boccaccio A, Dibattista M, Montani G, Tirindelli R, Menini A. 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 2010; 588:4189-204; PMID:20837642; http://dx.doi.org/10.1113/jphysiol.2010.194407
61. Kleene SJ. Origin of the chloride current in olfactory transduction. Neuron 1993; 11:123-32; PMID:8393322; http://dx.doi.org/10.1016/0896-6273(93)90276-W
62. Duran C, Thompson CH, Xiao Q, Hartzell HC. Chloride channels: often enigmatic, rarely predictable. Annu Rev Physiol 2010; 72:95-121; PMID:19827947; http://dx.doi.org/10.1146/annurev-physiol-021909-135811
63. Yang C, Delay RJ. Calcium-activated chloride current amplifies the response to urine in mouse vomeronasal sensory neurons. J Gen Physiol 2010; 135:3-13; PMID:20038523; http://dx.doi.org/10.1085/jgp.200910265
64. Kim S, Ma L, Yu CR. Requirement of calcium-activated chloride channels in the activation of mouse vomeronasal neurons. Nat Commun 2011; 2:365; PMID:21694713; http://dx.doi.org/10.1038/ncomms1368
65. Dibattista M, Amjad A, Maurya DK, Sagheddu C, Montani G, Tirindelli R, Menini A. Calcium-activated chloride channels in the apical region of mouse vomeronasal sensory neurons. J Gen Physiol 2012; 140:3-15; PMID:22732308; http://dx.doi.org/10.1085/jgp.201210780
66. Amjad A, Hernandez-Clavijo A, Pifferi S, Maurya DK, Boccaccio A, Franzot J, Rock J, Menini A. Conditional knockout of TMEM16A/anoctamin1 abolishes the calcium-activated chloride current in mouse vomeronasal sensory neurons. J Gen Physiol 2015; 145:285-301; PMID:25779870; http://dx.doi.org/10.1085/jgp.201411348
67. Hartzell C, Qu Z, Wei R, Mann W, Fischmeister R. Molecular physiology of calcium-activated chloride channels. speaker abstracts. J Gen Physiol 2003; 122:1a-46a; http://dx.doi.org/10.1085/jgp.20031221abstracts
68. Pifferi S, Dibattista M, Sagheddu C, Boccaccio A, Al Qteishat A, Ghirardi F, Tirindelli R, Menini A. Calcium-activated chloride currents in olfactory sensory neurons from mice lacking bestrophin-2. J Physiol 2009; 587:4265-79; PMID:19622610; http://dx.doi.org/10.1113/jphysiol.2009.176131
69. Yu K, Duran C, Qu Z, Cui YY, Hartzell HC. Explaining calcium-dependent gating of anoctamin-1 chloride channels requires a revised topologynovelty and significance. Circ Res 2012; 110:990-9; PMID:22394518; http://dx.doi.org/10.1161/CIRCRESAHA.112.264440
70. Brunner JD, Lim NK, Schenck S, Duerst A, Dutzler R. X-ray structure of a calcium-activated TMEM16 lipid scramblase. Nature 2014; 516:207-12; PMID:25383531; http://dx.doi.org/10.1038/nature13984
71. Pedemonte N, Galietta LJV. Structure and function of TMEM16 proteins (Anoctamins). Physiol Rev 2014; 94:419-59; PMID:24692353; http://dx.doi.org/10.1152/physrev.00039.2011
72. Picollo A, Malvezzi M, Accardi A. TMEM16 proteins: unknown structure and confusing functions. J Mol Biol 2015; 427:94-105; PMID:25451786; http://dx.doi.org/10.1016/j.jmb.2014.09.028
73. Pifferi S, Dibattista M, Menini A. TMEM16B induces chloride currents activated by calcium in mammalian cells. Pflüg Arch Eur J Physiol 2009; 458:1023-38; http://dx.doi.org/10.1007/s00424-009-0684-9
74. Stöhr H, Heisig JB, Benz PM, Schöberl S, Milenkovic VM, Strauss O, Aartsen WM, Wijnholds J, Weber BHF, Schulz HL. TMEM16B, A novel protein with calcium-dependent chloride channel activity, associates with a presynaptic protein complex in photoreceptor terminals. J Neurosci 2009; 29:6809-18; PMID:19474308; http://dx.doi.org/10.1523/JNEUROSCI.5546-08.2009
75. Stephan AB, Shum EY, Hirsh S, Cygnar KD, Reisert J, Zhao H. ANO2 is the cilial calcium-activated chloride channel that may mediate olfactory amplification. Proc Natl Acad Sci 2009; 106:11776-81; PMID:19561302; http://dx.doi.org/10.1073/pnas.0903304106
76. Mayer U, Küller A, Daiber PC, Neudorf I, Warnken U, Schnölzer M, Frings S, Möhrlen F. The proteome of rat olfactory sensory cilia. Proteomics 2009; 9:322-34; PMID:19086097; http://dx.doi.org/10.1002/pmic.200800149
77. Yu T-T, McIntyre JC, Bose SC, Hardin D, Owen MC, McClintock TS. Differentially expressed transcripts from phenotypically identified olfactory sensory neurons. J Comp Neurol 2005; 483:251-62; PMID:15682396; http://dx.doi.org/10.1002/cne.20429
78. Hengl T, Kaneko H, Dauner K, Vocke K, Frings S, Möhrlen F. Molecular components of signal amplification in olfactory sensory cilia. Proc Natl Acad Sci 2010; 107:6052-7; PMID:20231443; http://dx.doi.org/10.1073/pnas.0909032107
79. Rasche S, Toetter B, Adler J, Tschapek A, Doerner JF, Kurtenbach S, Hatt H, Meyer H, Warscheid B, Neuhaus EM. Tmem16b is Specifically Expressed in the Cilia of Olfactory Sensory Neurons. Chem Senses 2010; 35:239-45; PMID:20100788; http://dx.doi.org/10.1093/chemse/bjq007
80. Henkel B, Drose DR, Ackels T, Oberland S, Spehr M, Neuhaus EM. Co-expression of anoctamins in cilia of olfactory sensory neurons. Chem Senses 2015; 40:73-87; PMID:25500808; http://dx.doi.org/10.1093/chemse/bju061
81. Billig GM, Pál B, Fidzinski P, Jentsch TJ. Ca2+-activated Cl- currents are dispensable for olfaction. Nat Neurosci 2011; 14:763-9; PMID:21516098; http://dx.doi.org/10.1038/nn.2821
82. Maurya DK, Menini A. Developmental expression of the calcium-activated chloride channels TMEM16A and TMEM16B in the mouse olfactory epithelium. Dev Neurobiol 2014; 74:657-75; PMID:24318978; http://dx.doi.org/10.1002/dneu.22159
83. Maurya DK, Henriques T, Marini M, Pedemonte N, Galietta LJV, Rock JR, Harfe BD, Menini A. Development of the olfactory epithelium and nasal glands in TMEM16A−/− and TMEM16A+/+ mice. PloS One 2015; 10:e0129171; PMID:26067252; http://dx.doi.org/10.1371/journal.pone.0129171
84. Tien J, Lee HY, Minor DL, Jan YN, Jan LY. Identification of a dimerization domain in the TMEM16A calcium-activated chloride channel (CaCC). Proc Natl Acad Sci 2013; 110:6352-7; PMID:23576756; http://dx.doi.org/10.1073/pnas.1303672110
85. Saidu SP, Stephan AB, Talaga AK, Zhao H, Reisert J. Channel properties of the splicing isoforms of the olfactory calcium-activated chloride channel Anoctamin 2. J Gen Physiol 2013; 141:691-703; PMID:23669718; http://dx.doi.org/10.1085/jgp.201210937
86. Pifferi S, Cenedese V, Menini A. Anoctamin 2/TMEM16B: a calcium-activated chloride channel in olfactory transduction. Exp Physiol 2012; 97:193-9; PMID:21890523; http://dx.doi.org/10.1113/expphysiol.2011.058230
87. Pietra G, Dibattista M, Menini A, Reisert J, Boccaccio A. The Ca2+-activated Cl− channel TMEM16B regulates action potential firing and axonal targeting in olfactory sensory neurons. J Gen Physiol 2016; 148:293-311; PMID:27619419; http://dx.doi.org/10.1085/jgp.201611622
88. Huang WC, Xiao S, Huang F, Harfe BD, Jan YN, Jan LY. Calcium-activated chloride channels (CaCCs) regulate action potential and synaptic response in hippocampal neurons. Neuron 2012; 74:179-92; PMID:22500639; http://dx.doi.org/10.1016/j.neuron.2012.01.033
89. Zhang W, Schmelzeisen S, Parthier D, Frings S, Möhrlen F. Anoctamin calcium-activated chloride channels may modulate inhibitory transmission in the cerebellar cortex. PLOS One 2015; 10:e0142160; PMID:26558388; http://dx.doi.org/10.1371/journal.pone.0142160
90. Ha GE, Lee J, Kwak H, Song K, Kwon J, Jung SY, Hong J, Chang GE, Hwang EM, Shin HS, et al. The Ca(2+)-activated chloride channel anoctamin-2 mediates spike-frequency adaptation and regulates sensory transmission in thalamocortical neurons. Nat Commun 2016; 7:13791; PMID:27991499; http://dx.doi.org/10.1038/ncomms13791
91. Lynch JW, Barry PH. Action potentials initiated by single channels opening in a small neuron (rat olfactory receptor). Biophys J 1989; 55:755-68; PMID:2470428; http://dx.doi.org/10.1016/S0006-3495(89)82874-7
92. Trotier D. Intensity coding in olfactory receptor cells. Semin Cell Biol 1994; 5:47-54; PMID:7514456; http://dx.doi.org/10.1006/scel.1994.1007
93. Lynch JW, Barry PH. Inward rectification in rat olfactory receptor neurons. Proc Biol Sci 1991; 243:149-53; PMID:1676518; http://dx.doi.org/10.1098/rspb.1991.0024
94. Dibattista M, Reisert J. The odorant receptor-dependent role of olfactory marker protein in olfactory receptor neurons. J Neurosci 2016; 36:2995-3006; PMID:26961953; http://dx.doi.org/10.1523/JNEUROSCI.4209-15.2016
95. Rospars JP, Lansky P, Chaput M, Duchamp-Viret P. Competitive and noncompetitive odorant interactions in the early neural coding of odorant mixtures. J Neurosci 2008; 28:2659-66; PMID:18322109; http://dx.doi.org/10.1523/JNEUROSCI.4670-07.2008
96. Gesteland RC, Sigwart CD. Olfactory receptor units—a mammalian preparation. Brain Res 1977; 133:144-9; PMID:902082; http://dx.doi.org/10.1016/0006-8993(77)90055-5
97. Firestein S, Picco C, Menini A. The relation between stimulus and response in olfactory receptor cells of the tiger salamander. J Physiol 1993; 468:1-10; PMID:8254501; http://dx.doi.org/10.1113/jphysiol.1993.sp019756
98. Ponissery Saidu S, Dibattista M, Matthews HR, Reisert J. Odorant-induced responses recorded from olfactory receptor neurons using the suction pipette technique. J Vis Exp JoVE 2012; e3862; PMID:22508037
99. Reisert J. Origin of basal activity in mammalian olfactory receptor neurons. J Gen Physiol 2010; 136:529-40; PMID:20974772; http://dx.doi.org/10.1085/jgp.201010528
100. Connelly T, Savigner A, Ma M. Spontaneous and sensory-evoked activity in mouse olfactory sensory neurons with defined odorant receptors. J Neurophysiol 2013; 110:55-62; PMID:23596334; http://dx.doi.org/10.1152/jn.00910.2012
101. Araneda RC, Kini AD, Firestein S. The molecular receptive range of an odorant receptor. Nat Neurosci 2000; 3:1248-55; PMID:11100145; http://dx.doi.org/10.1038/81774
102. Kurland MD, Newcomer MB, Peterlin Z, Ryan K, Firestein S, Batista VS. Discrimination of saturated aldehydes by the rat I7 olfactory receptor. Biochemistry (Mosc) 2010; 49:6302-4; http://dx.doi.org/10.1021/bi100976w
103. Zou D-J, Chesler A, Firestein S. How the olfactory bulb got its glomeruli: a just so story? Nat Rev Neurosci 2009; 10:611-8; PMID:19584894; http://dx.doi.org/10.1038/nrn2666
104. Lorenzon P, Redolfi N, Podolsky MJ, Zamparo I, Franchi SA, Pietra G, Boccaccio A, Menini A, Murthy VN, Lodovichi C. Circuit formation and function in the olfactory bulb of mice with reduced spontaneous afferent activity. J Neurosci 2015; 35:146-60; PMID:25568110; http://dx.doi.org/10.1523/JNEUROSCI.0613-14.2015
105. Imai T, Suzuki M, Sakano H. Odorant receptor-derived cAMP signals direct axonal targeting. Science 2006; 314:657-61; PMID:16990513; http://dx.doi.org/10.1126/science.1131794
106. Nakashima A, Takeuchi H, Imai T, Saito H, Kiyonari H, Abe T, Chen M, Weinstein LS, Yu CR, Storm DR, et al. Agonist-independent GPCR activity regulates anterior-posterior targeting of olfactory sensory neurons. Cell 2013; 154:1314-25; PMID:24034253; http://dx.doi.org/10.1016/j.cell.2013.08.033
107. Takeuchi H, Sakano H. Neural map formation in the mouse olfactory system. Cell Mol Life Sci CMLS 2014; 71:3049-57; PMID:24638094; http://dx.doi.org/10.1007/s00018-014-1597-0
108. Zapiec B, Bressel OC, Khan M, Walz A, Mombaerts P. Neuropilin-1 and the positions of glomeruli in the mouse olfactory bulb. eNeuro 2016; 3; PMID:27844052; http://dx.doi.org/10.1523/ENEURO.0123-16.2016
109. Movahedi K, Grosmaitre X, Feinstein P. Odorant receptors can mediate axonal identity and gene choice via cAMP-independent mechanisms. Open Biol [Internet] 2016 [cited 2016 Dec 24]; 6:pii: 160018. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967819/; PMID:27466441; http://dx.doi.org/10.1098/rsob.160018
110. Assens A, Dal Col J, Njoku A, Dietschi Q, Kan C, Feinstein P, Carleton A, Rodriguez I. Alteration of Nrp1 signaling at different stages of olfactory neuron maturation promotes glomerular shifts along distinct axes in the olfactory bulb. Dev Camb Engl 2016; 143(20):3817-25