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PMID: 21516098 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Ca2+-activated Cl− currents are dispensable for olfaction.

Nature neuroscience ·Vol. 14 ·No. 6 ·2011-06-00 ·Pages 763-9

Billig GM, Pál B, Fidzinski P, Jentsch TJ

Abstract

Canonical olfactory signal transduction involves the activation of cyclic AMP-activated cation channels that depolarize the cilia of receptor neurons and raise intracellular calcium. Calcium then activates Cl(-) currents that may be up to tenfold larger than cation currents and are believed to powerfully amplify the response. We identified Anoctamin2 (Ano2, also known as TMEM16B) as the ciliary Ca(2+)-activated Cl(-) channel of olfactory receptor neurons. Ano2 is expressed in the main olfactory epithelium (MOE) and in the vomeronasal organ (VNO), which also expresses the related Ano1 channel. Disruption of Ano2 in mice virtually abolished Ca(2+)-activated Cl(-) currents in the MOE and VNO. Ano2 disruption reduced fluid-phase electro-olfactogram responses by only ∼40%, did not change air-phase electro-olfactograms and did not reduce performance in olfactory behavioral tasks. In contrast with the current view, cyclic nucleotide-gated cation channels do not need a boost by Cl(-) channels to achieve near-physiological levels of olfaction.

MeSH Terms
Animals Anoctamins Calcium/metabolism Chloride Channels/deficiency,genetics,metabolism Mice Mice, 129 Strain Mice, Inbred C57BL Mice, Knockout Olfactory Receptor Neurons/metabolism Signal Transduction/genetics Smell/genetics Vomeronasal Organ/metabolism
Chemicals
ANO2 protein, mouse Anoctamins Chloride Channels Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Billig Gwendolyn M
Leibniz-Institut für Molekulare Pharmakologie (FMP)/Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Germany.
Pál Balázs
Fidzinski Pawel
Jentsch Thomas J
References (48)
48 references, click to expand
  1. The electrochemical basis of odor transduction in vertebrate olfactory cilia.
    Chem Senses. 2008 Nov;33(9):839-59 PMID: 18703537
  2. Transmembrane protein 16A (TMEM16A) is a Ca2+-regulated Cl- secretory channel in mouse airways.
    J Biol Chem. 2009 May 29;284(22):14875-80 PMID: 19363029
  3. Ion changes in spreading ischaemia induce rat middle cerebral artery constriction in the absence of NO.
    Brain. 2005 Sep;128(Pt 9):2042-51 PMID: 15901647
  4. Peripheral olfactory projections are differentially affected in mice deficient in a cyclic nucleotide-gated channel subunit.
    Neuron. 2000 Apr;26(1):81-91 PMID: 10798394
  5. General anosmia caused by a targeted disruption of the mouse olfactory cyclic nucleotide-gated cation channel.
    Neuron. 1996 Oct;17(4):681-93 PMID: 8893025
  6. Temporal development of cyclic nucleotide-gated and Ca2+ -activated Cl- currents in isolated mouse olfactory sensory neurons.
    J Neurophysiol. 2007 Jul;98(1):153-60 PMID: 17460108
  7. 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 Nov 1;588(Pt 21):4189-204 PMID: 20837642
  8. Chloride accumulation in mammalian olfactory sensory neurons.
    J Neurosci. 2004 Sep 8;24(36):7931-8 PMID: 15356206
  9. Performance of mice in an automated olfactometer: odor detection, discrimination and odor memory.
    Chem Senses. 1999 Dec;24(6):637-45 PMID: 10587496
  10. Ionic conductances in sustentacular cells of the mouse olfactory epithelium.
    J Physiol. 2005 Feb 1;562(Pt 3):785-99 PMID: 15611020
  11. Neuronal Ca2+ -activated Cl- channels--homing in on an elusive channel species.
    Prog Neurobiol. 2000 Feb;60(3):247-89 PMID: 10658643
  12. Absence of adenylyl cyclase 3 perturbs peripheral olfactory projections in mice.
    J Neurosci. 2007 Jun 20;27(25):6675-83 PMID: 17581954
  13. Immunological studies of the rat olfactory marker protein.
    J Neurochem. 1975 Jun;24(6):1101-6 PMID: 805214
  14. A cyclic nucleotide-gated conductance in olfactory receptor cilia.
    Nature. 1987 Jan 29-Feb 4;325(6103):442-4 PMID: 3027574
  15. Persistence of the olfactory receptor current in a wide variety of extracellular environments.
    J Neurophysiol. 1996 Apr;75(4):1386-91 PMID: 8727385
  16. Neuronal chloride accumulation in olfactory epithelium of mice lacking NKCC1.
    J Neurophysiol. 2006 Mar;95(3):2003-6 PMID: 16319203
  17. A depolarizing chloride current contributes to chemoelectrical transduction in olfactory sensory neurons in situ.
    J Neurosci. 1998 Sep 1;18(17):6623-30 PMID: 9712634
  18. Mechanism of the excitatory Cl- response in mouse olfactory receptor neurons.
    Neuron. 2005 Feb 17;45(4):553-61 PMID: 15721241
  19. Electroolfactogram responses from organotypic cultures of the olfactory epithelium from postnatal mice.
    Chem Senses. 2008 Apr;33(4):397-404 PMID: 18303030
  20. Tmem16A encodes the Ca2+-activated Cl- channel in mouse submandibular salivary gland acinar cells.
    J Biol Chem. 2010 Apr 23;285(17):12990-3001 PMID: 20177062
  21. Predicted profiles of ion concentrations in olfactory cilia in the steady state.
    Biophys J. 2001 Apr;80(4):1712-21 PMID: 11259285
  22. TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity.
    Science. 2008 Oct 24;322(5901):590-4 PMID: 18772398
  23. Analyzing responses of mouse olfactory sensory neurons using the air-phase electroolfactogram recording.
    J Vis Exp. 2010 Mar 02;(37): PMID: 20197755
  24. TMEM16B, a novel protein with calcium-dependent chloride channel activity, associates with a presynaptic protein complex in photoreceptor terminals.
    J Neurosci. 2009 May 27;29(21):6809-18 PMID: 19474308
  25. A cre-transgenic mouse strain for the ubiquitous deletion of loxP-flanked gene segments including deletion in germ cells.
    Nucleic Acids Res. 1995 Dec 25;23(24):5080-1 PMID: 8559668
  26. TMEM16A confers receptor-activated calcium-dependent chloride conductance.
    Nature. 2008 Oct 30;455(7217):1210-5 PMID: 18724360
  27. Electrophysiological properties and modeling of murine vomeronasal sensory neurons in acute slice preparations.
    Chem Senses. 2006 Jun;31(5):425-35 PMID: 16547196
  28. Calcium-activated chloride currents in olfactory sensory neurons from mice lacking bestrophin-2.
    J Physiol. 2009 Sep 1;587(Pt 17):4265-79 PMID: 19622610
  29. Mice lacking NKCC1 have normal olfactory sensitivity.
    Physiol Behav. 2008 Jan 28;93(1-2):44-9 PMID: 17719611
  30. Bestrophin-2 is a candidate calcium-activated chloride channel involved in olfactory transduction.
    Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12929-34 PMID: 16912113
  31. Calcium-activated chloride conductance in frog olfactory cilia.
    J Neurosci. 1991 Nov;11(11):3624-9 PMID: 1941099
  32. Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract.
    Am J Physiol Gastrointest Liver Physiol. 2009 Jun;296(6):G1370-81 PMID: 19372102
  33. The Ca-activated Cl channel and its control in rat olfactory receptor neurons.
    J Gen Physiol. 2003 Sep;122(3):349-63 PMID: 12939394
  34. ANO2 is the cilial calcium-activated chloride channel that may mediate olfactory amplification.
    Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11776-81 PMID: 19561302
  35. The native rat olfactory cyclic nucleotide-gated channel is composed of three distinct subunits.
    J Neurosci. 1999 Jul 1;19(13):5332-47 PMID: 10377344
  36. Molecular components of signal amplification in olfactory sensory cilia.
    Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):6052-7 PMID: 20231443
  37. Expression cloning of TMEM16A as a calcium-activated chloride channel subunit.
    Cell. 2008 Sep 19;134(6):1019-29 PMID: 18805094
  38. Co-existence of cationic and chloride components in odorant-induced current of vertebrate olfactory receptor cells.
    Nature. 1993 May 6;363(6424):71-4 PMID: 7683113
  39. Nonlinear amplification by calcium-dependent chloride channels in olfactory receptor cells.
    Nature. 1993 Nov 18;366(6452):283-6 PMID: 8232590
  40. TMEM16B induces chloride currents activated by calcium in mammalian cells.
    Pflugers Arch. 2009 Oct;458(6):1023-38 PMID: 19475416
  41. Odors detected by mice deficient in cyclic nucleotide-gated channel subunit A2 stimulate the main olfactory system.
    J Neurosci. 2004 Apr 7;24(14):3703-10 PMID: 15071119
  42. Subsystem organization of the mammalian sense of smell.
    Annu Rev Physiol. 2009;71:115-40 PMID: 18808328
  43. Tmem16b is specifically expressed in the cilia of olfactory sensory neurons.
    Chem Senses. 2010 Mar;35(3):239-45 PMID: 20100788
  44. Importance of the CNGA4 channel gene for odor discrimination and adaptation in behaving mice.
    Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4299-304 PMID: 12649326
  45. Effects of channel modulators on cloned large-conductance calcium-activated potassium channels.
    Mol Pharmacol. 1996 Jul;50(1):206-17 PMID: 8700114
  46. A common 253-kb deletion involving VWF and TMEM16B in German and Italian patients with severe von Willebrand disease type 3.
    J Thromb Haemost. 2007 Apr;5(4):722-8 PMID: 17371490
  47. Origin of the chloride current in olfactory transduction.
    Neuron. 1993 Jul;11(1):123-32 PMID: 8393322
  48. Mechanisms of neuronal chloride accumulation in intact mouse olfactory epithelium.
    J Physiol. 2007 Sep 15;583(Pt 3):1005-20 PMID: 17656441
Article Info
Journal
Nature neuroscience
Abbr.
Nat Neurosci
ISSN
1546-1726
DOI
10.1038/nn.2821
Published
2011-06-00
Epub
2011-00-24
Pages
763-9
Language
English
Region
United States
NLM ID
9809671
Subset
IM
External Links
PubMed source DOI: 10.1038/nn.2821 View journal details
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