Anoctamin 2/TMEM16B: a calcium‐activated chloride channel in olfactory transduction

Abstract

In vertebrate olfactory transduction, a Ca2+ -dependent Cl − efflux greatly amplifies the odorant response. 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. The Ca 2+ activates a Cl − current that, in the presence of a maintained elevated intracellular Cl − concentration, produces an efflux of Cl − ions and amplifies the depolarization. In this review, we summarize evidence supporting the hypothesis that anoctamin 2/TMEM16B is the main, or perhaps the only, constituent of the Ca 2+ -activated Cl − channels involved in olfactory transduction. Indeed, studies from several laboratories have shown that anoctamin 2/TMEM16B is expressed in the ciliary layer of the olfactory epithelium, that there are remarkable functional similarities between currents in olfactory sensory neurons and in HEK 293 cells transfected with anoctamin 2/TMEM16B, and that knockout mice for anoctamin 2/TMEM16B did not show any detectable Ca 2+ -activated Cl − current. Finally, we discuss the involvement of Ca 2+ -activated Cl − channels in the transduction process of vomeronasal sensory neurons and the physiological role of these channels in olfaction.

Interactions between permeation and gating in the TMEM16B/anoctamin2 calcium-activated chloride channel

“…The standard intracellular solution contained (mM) 140 CsCl, 10 HEPES, 10 HEDTA (or 5 EGTA), pH 7.2, and no added Ca 2+ for the nominally 0 Ca 2+ solution, or various amounts of CaCl 2 , as calculated with the program WinMAXC (C. Patton, Stanford University, Stanford, CA), to photoreceptors (Stöhr et al, 2009;Billig et al, 2011;Dauner et al, 2013), in hippocampal cells (Huang et al, 2012b), in the cilia of olfactory sensory neurons, and in the microvilli of vomeronasal sensory neurons (Stephan et al, 2009;Hengl et al, 2010;Rasche et al, 2010;Sagheddu et al, 2010;Billig et al, 2011;Dauner et al, 2012;Dibattista et al, 2012;Maurya and Menini, 2013). Studies with knockout mice for TMEM16A or TMEM16B (Rock and Harfe, 2008;Billig et al, 2011) or knockdown of these channels further confirmed a reduction in CaCC activity (Flores et al, 2009;Galietta, 2009;Hartzell et al, 2009;Huang et al, 2012a;Kunzelmann et al, 2012a,b;Pifferi et al, 2012;Sanders et al, 2012;Scudieri et al, 2012).…”

The anoctamin family: TMEM16A and TMEM16B as calcium‐activated chloride channels

“…The biophysical properties and pattern of expression of TMEM16B indicate that this protein is the main component of the CaCC in olfactory sensory neurons (Pifferi et al 2011). A recently developed Tmem16B knockout mouse shows a severe reduction in the Ca 2+ -dependent Cl − conductance of olfactory neurons (Billig et al 2011); however, these animals are still able to sense olfactory stimuli.…”

The anoctamin (TMEM16) gene family: calcium‐activated chloride channels come of age

“…Anna Menini (International School for Advanced Studies, Italy) gave a lovely presentation on the importance of CaCCs in olfaction (Pifferi et al 2012). Odorant molecules bind to odoursensing receptors (OSRs), leading to an increase in calcium entry that activates CaCC current that amplifies the depolarization of the OSR cells.…”