title: Ca2+-activated Cl− currents are dispensable for olfaction.
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.
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP)/Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Germany.
authors.forename: Gwendolyn M
authors.initials: GM
authors.lastname: Billig
authors.forename: Balázs
authors.initials: B
authors.lastname: Pál
authors.forename: Pawel
authors.initials: P
authors.lastname: Fidzinski
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Jentsch
mesh_terms: D000818:Animals; D000075368:Anoctamins; D002118:Calcium / Q000378:metabolism*; D018118:Chloride Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018034:Olfactory Receptor Neurons / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D012903:Smell / Q000235:genetics; D019147:Vomeronasal Organ / Q000378:metabolism*
chemical_list: C532161:ANO2 protein, mouse; D000075368:Anoctamins; D018118:Chloride Channels; D002118:Calcium