title: Calcium-activated chloride currents in olfactory sensory neurons from mice lacking bestrophin-2.
abstract: Olfactory sensory neurons use a chloride-based signal amplification mechanism to detect odorants. The binding of odorants to receptors in the cilia of olfactory sensory neurons activates a transduction cascade that involves the opening of cyclic nucleotide-gated channels and the entry of Ca(2+) into the cilia. Ca(2+) activates a Cl(-) current that produces an efflux of Cl(-) ions and amplifies the depolarization. The molecular identity of Ca(2+)-activated Cl(-) channels is still elusive, although some bestrophins have been shown to function as Ca(2+)-activated Cl(-) channels when expressed in heterologous systems. In the olfactory epithelium, bestrophin-2 (Best2) has been indicated as a candidate for being a molecular component of the olfactory Ca(2+)-activated Cl(-) channel. In this study, we have analysed mice lacking Best2. We compared the electrophysiological responses of the olfactory epithelium to odorant stimulation, as well as the properties of Ca(2+)-activated Cl(-) currents in wild-type (WT) and knockout (KO) mice for Best2. Our results confirm that Best2 is expressed in the cilia of olfactory sensory neurons, while odorant responses and Ca(2+)-activated Cl(-) currents were not significantly different between WT and KO mice. Thus, Best2 does not appear to be the main molecular component of the olfactory channel. Further studies are required to determine the function of Best2 in the cilia of olfactory sensory neurons.
authors.affiliation: International School for Advanced Studies, Scuola Internazionale Superiore di Studi Avanzati, SISSA, and Italian Institute of Technology, SISSA Unit, Trieste, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Pifferi
authors.forename: Michele
authors.initials: M
authors.lastname: Dibattista
authors.forename: Claudia
authors.initials: C
authors.lastname: Sagheddu
authors.forename: Anna
authors.initials: A
authors.lastname: Boccaccio
authors.forename: Ahmed
authors.initials: A
authors.lastname: Al Qteishat
authors.forename: Filippo
authors.initials: F
authors.lastname: Ghirardi
authors.forename: Roberto
authors.initials: R
authors.lastname: Tirindelli
authors.forename: Anna
authors.initials: A
authors.lastname: Menini
mesh_terms: D000818:Animals; D000075002:Bestrophins; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D009297:Nasal Mucosa / Q000502:physiology*; D018034:Olfactory Receptor Neurons / Q000502:physiology*; D012903:Smell / Q000502:physiology*
chemical_list: C497463:Best2 protein, mouse; D000075002:Bestrophins; D018118:Chloride Channels; D002712:Chlorides; D005136:Eye Proteins