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Ca2+-activated Cl− currents are dispensable for olfaction

Nature Neuroscience volume 14, pages 763–769 (2011)Cite this article

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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 Ca2+-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 Ca2+-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.

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Figure 1: Immunoblot analysis of Ano2 expression.
Figure 2: Ano2 localizes to sensory protrusions in olfactory epithelia.
Figure 3: Ano2 and Ano1 are co-expressed in the VNO but not in the MOE.
Figure 4: The olfactory bulb in Ano2−/− and Ano2+/+ mice.
Figure 5: Effect of Ano2 disruption on Ca2+-activated Cl− currents.
Figure 6: Response of isolated olfactory receptor neurons to photoreleased Ca2+ or 8-Br-cAMP.
Figure 7: EOGs from the MOE.
Figure 8: Ano2 disruption affected neither odor discrimination nor olfactory sensitivity.

Change history

  • 08 May 2011

    In the version of this article initially published online, there were two errors in Figure 7 and one in the author affiliations. The units given in Figure 7e for the y axis and for the concentration of mix1 were incorrect; the correct units are µV and mM, respectively. The abbreviation in the affiliations for the Max-Delbrück-Centrum für Molekulare Medizin was incorrect; the correct abbreviation is MDC. The errors have been corrected for the print, PDF and HTML versions of this article.

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Acknowledgements

We thank P. Mombaerts (Max Planck Institute for Biophysics) for providing Cnga2−, P2-IRES-tauLacZ and M72-IRES-tauLacZ mice, V. Hagen (FMP) for caged 8-Br-cAMP, I. Zarour and U. Heinemann (Charité) for help with ion-selective microelectrodes, S. Jabs and L. Leisle for help with flash photolysis, P. Mombaerts and B. Schroeder (MDC) for helpful discussions and N. Krönke and F. Binder for technical assistance. This work was supported, in part, by the Prix Louis-Jeantet de Médecine to T.J.J.

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Authors and Affiliations

  1. Leibniz-Institut für Molekulare Pharmakologie (FMP)/Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Germany

    Gwendolyn M Billig, Balázs Pál, Pawel Fidzinski & Thomas J Jentsch

  2. Graduate Program of the Freie Universität Berlin, Berlin, Germany

    Gwendolyn M Billig

  3. NeuroCure Cluster of Excellence, Charité, Berlin, Germany

    Thomas J Jentsch

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  1. Gwendolyn M Billig
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Contributions

G.M.B. generated Ano2−/− mice and Ano2 antibodies, designed, performed and evaluated expression analysis and immunohistochemistry, olfactometry and mouse behavioral studies and wrote the paper. B.P. designed, performed and evaluated patch-clamp analysis, EOG and ion-selective microelectrode measurements and wrote the paper. B.P. and P.F. designed, performed and evaluated flash-photolysis experiments. T.J.J. initiated the project, designed and evaluated experiments and wrote the paper.

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Correspondence to Thomas J Jentsch.

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Billig, G., Pál, B., Fidzinski, P. et al. Ca2+-activated Cl− currents are dispensable for olfaction. Nat Neurosci 14, 763–769 (2011). https://doi.org/10.1038/nn.2821

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