Olfaction starts at the olfactory cilia of the olfactory receptor cells (ORCs). This site mediating the olfactory transduction exhibits a fine cylindrical structure having 100-200 nm diameter and length of several tens of micrometers. All molecular factors needed for the signal conversion are equipped in such a fine tubing; namely, receptor protein, G protein, adenylyl cyclase, cyclic nucleotide-gated (CNG), and Ca2+-activated Cl (Cl(Ca)) channels. Cytoplasmic cAMP and Ca2+ play roles for the second messengers within the cilia. In the present study, we examined the effect of off-flavors generated in wide varieties of foods/beverages on the transduction current using the isolated newt ORCs and human sensory test.The experiments were performed under the latest ethical guidelines for animal/human experimentation at Osaka University. Ciliary current responses were obtained by the photolysis of cytoplasmic caged cAMP under the whole-cell recording configuration (voltage clamp, Vh=-50mV) (1). We show with human psycho-physical tests that TCA (known for a powerful off-flavor inducing the cork taint of wines) reduces flavors of wines with very low concentration (10 ppt, =47 pM). In parallel, it was shown that TCA suppressed potently transduction currents of single newt ORCs. The rank order of potency of CNG suppression by TCA analogues or precursors was identical to that of the human detection of the corresponding off-flavors. For instance, suppression ratio of TCA equivalent to 2,4,6-tribromoanisole (TBA), which is much greater than 2,4,6-trichlorophenol (TCP; precursor of TCA), suggesting that TCA suppression of CNG channels is related to cork taint. TCA exerted a much more potent suppressive effect on CNG channels (100-1,000-fold) than other known olfactory masking agents called geraniol that have been widely used in perfumery. It was also more potent than a well-known specific CNG channel blocker, L-cis-diltiazem. Furthermore, TCA suppression of transduction current was detected even with atto-molar (aM) concentration (2). In the presentation, we show experimental evidence to discuss the molecular mechanism expressing such super-efficiency. The findings not only reveal a likely mechanism of flavor loss of foods/beverages, but also suggest certain molecular structures as possible olfactory masking agents and powerful channel suppressors.
Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, PC106
Poster Communications: Modulation of CNG channel activity in the olfactory cilia
H. Takeuchi1, T. Kurahashi1
1. Graduate School of Frontier Biosciences, Osaka University, Toyonaka, Osaka, Japan.
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Where applicable, experiments conform with Society ethical requirements.