Ca2+-Activated Cl− Channels of the ClCa Family Express in the Cilia of a Subset of Rat Olfactory Sensory Neurons

Abstract

The Ca2+-activated Cl− channel is considered a key constituent of odor transduction. Odorant binding to a specific receptor in the cilia of olfactory sensory neurons (OSNs) triggers a cAMP cascade that mediates the opening of a cationic cyclic nucleotide-gated channel (CNG), allowing Ca2+ influx. Ca2+ ions activate Cl− channels, generating a significant Cl− efflux, with a large contribution to the receptor potential. The Anoctamin 2 channel (ANO2) is a major constituent of the Cl− conductance, but its knock-out has no impairment of behavior and only slightly reduces field potential odorant responses of the olfactory epithelium. Likely, an additional Ca2+-activated Cl− channel of unknown molecular identity is also involved. In addition to ANO2, we detected two members of the ClCa family of Ca2+-activated Cl− channels in the rat olfactory epithelium, ClCa4l and ClCa2. These channels, also expressed in the central nervous system, may correspond to odorant transduction channels. Whole Sprague Dawley olfactory epithelium nested RT-PCR and single OSNs established that the mRNAs of both channels are expressed in OSNs. Real time RT-PCR and full length sequencing of amplified ClCa expressed in rat olfactory epithelium indicated that ClCa4l is the most abundant. Immunoblotting with an antibody recognizing both channels revealed immunoreactivity in the ciliary membrane. Immunochemistry of olfactory epithelium and OSNs confirmed their ciliary presence in a subset of olfactory sensory neurons. The evidence suggests that ClCa4l and ClCa2 might play a role in odorant transduction in rat olfactory cilia.

NaV1.5 sodium channel window currents contribute to spontaneous firing in olfactory sensory neurons

“…3, A-C). The presence of IP 3 R3-positive nonsensory, microvillous epithelial cells in the apical compartment of the olfactory epithelium is documented elsewhere (Hegg et al 2010). This apical compartment also contains the apical dendrites and dendritic knobs of OSNs.…”

“…In the second transgenic line (MMRRC STOCK Itpr3tm1.1Rmnc) a tau-GFP construct (tauGFP) placed under the control of the Itpr3 regulatory elements is expressed by a population of nonneuronal microvillous cells situated high in the olfactory epithelium but that do not extend an axon to the olfactory bulb and are not OSNs (Hegg et al 2010). The animals were housed on a 14-h light cycle with access to standard chow ad libitum.…”

Assessment of the Olfactory Function in Italian Patients with Type 3 von Willebrand Disease Caused by a Homozygous 253 Kb Deletion Involving VWF and TMEM16B/ANO2

“…However, the role played by TMEM16B/ANO2 in olfaction is controversial. Indeed, knockout mice for TMEM16B did not show any difference in olfactory sensitivity compared with wild-type mice [ 24 ] suggesting that this protein may be dispensable for normal olfaction, although another study [ 27 ] indicated that additional members of the CLCA family may also participate in the process of olfactory transduction together with TMEM16B, and substitute TMEM16B when it is absent.…”

Ion Transporter NKCC1, Modulator of Neurogenesis in Murine Olfactory Neurons

“…A calcium-activated chloride channel (Clca2) (63) exhibited a higher FPKM value in the NKCC1-deficient transcriptome. This chloride channel is expressed in a subset of OSNs and may play a role in odorant transduction in cilia (64). Moreover, protocadherin 10 (Pcdh10), a gene with key roles in suppressing cell proliferation (65), displayed a higher FPKM value in NKCC1-deficient mice.…”