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.
Highlights
Olfactory transduction occurs in the cilia of olfactory sensory neurons (OSNs), where binding of odorant molecules to olfactory receptors triggers a cyclic AMP cascade
In the present work we demonstrate that mRNA transcripts for two members of the ClCa family, ClCa4l and ClCa2, are expressed in rat OSNs
We show that immunohistochemistry indicates that ClCa channel proteins are present in the chemosensory cilia of a subset of OSNs, opening the possibility that they contribute to the odorant transduction Cl2 conductance
Summary
Olfactory transduction occurs in the cilia of olfactory sensory neurons (OSNs), where binding of odorant molecules to olfactory receptors triggers a cyclic AMP cascade. Mediated by heterotrimeric G-protein, Golf, the receptor stimulates adenylyl cyclase type III, rapidly increasing cAMP. This nucleotide directly gates cyclic nucleotide-gated nonselective cation channels, CNG, mediating a Ca2+ and Na+ influx into the ciliary lumen that contributes to the depolarizing current [1]. The CNG channel has been extensively studied both molecularly as well as electrophysiologically [4]. It is made up of subunits (CNGA2, CNGB1b and CNGA4) that belong to the cyclicnucleotide gated channel family, whose other well characterized member is found in vertebrate photoreceptors, where it plays a paramount role in visual transduction [5]. Its biophysical features have only been partially characterized and a thorough pharmacological profile for this channel is unavailable
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