Ca2+-activated Cl ? channels are an important component of olfactory transduction. Odorant binding to odorant receptors in the cilia of olfactory sensory neurons (OSNs) leads to an increase of intraciliary Ca2+ concentration by Ca2+ entry through cyclic nucleotide-gated channels. Ca2+ activates a Cl ? channel that leads to an efflux of Cl ? from the cilia, contributing to the amplification of the OSN depolarization. The molecular identity of this Cl ? channel remains elusive. Recent evidences have indicated that bestrophins are able to form Ca2+-activated Cl ? channels channels in heterologous systems. Immunohistochemistry revealed that mBest2 was expressed on the cilia of OSNs, the site of olfactory transduction, and co-localized with the main subunit of cyclic nucleotide-gated channels, CNGA2. We performed a functional comparison of the properties of Ca2+-activated Cl ? channels from native channels expressed in dendritic knob/cilia of mouse OSNs with those induced by heterologous expression of mBest2 in HEK-293 cells. Even if the two channels did not display identical characteristics, they have many similar features such as the same anion permeability, the Ca2+ sensitivity in micromolar range and the same side-specific blockage of the two Cl ? channel blockers commonly used to inhibit the odorant-induced Ca2+-activated Cl ? channels in OSNs, niflumic acid and 4-acetamido-4’-isothiocyanato-stilben-2,2’-disulfonate (SITS). However electroolfactogram recording from mBest2 null mice showed a normal sensitivity to odorant stimulation. Therefore mBest2 is a good candidate for being a molecular component of the olfactory Ca2+-activated Cl ? channels but its precise role in olfactory transduction remains to be clarified.
Calcium Activated Chloride Channels In Olfactory Transduction [Tesi di dottorato]
Tesi di dottorato. | Lingua: en. | Paese: | BID: TD15088443
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