Olfactory cilia, regulation and control of olfaction

Abstract

The sense of smell is still considered a fuzzy sensation. Softly wafting aromas can stimulate the appetite and trigger memories; however, there are many unexplored aspects of its underlying mechanisms, and not all of these have been elucidated. Although the final sense of smell takes place in the brain, it is greatly affected during the preliminary stage, when odorants are converted into electrical signals. After signal conversion through ion channels in olfactory cilia, action potentials are generated through other types of ion channels located in the cell body. Spike trains through axons transmit this information as digital signals to the brain, however, before odorants are converted into digital electric signals, such as an action potential, modification of the transduction signal has already occurred. This review focuses on the early stages of olfactory signaling. Modification of signal transduction mechanisms and their effect on the human sense of smell through three characteristics (signal amplification, olfactory adaptation, and olfactory masking) produced by olfactory cilia, which is the site of signal transduction are being addressed in this review.

Keywords: Cl(Ca) channels; cyclic nucleotide‐gated channels; olfactory adaptation; olfactory cilia; olfactory masking; signal amplification.

FIGURE 1

Olfactory perception. (a) Nose and olfactory epithelium (OE) in a sagittal plane of human head. (b) Signal transmission from OE to olfactory bulb (OB). (c) Single olfactory receptor cell (ORC) and a single cilium. Transduction cascade in the cilia. OR, olfactory receptor protein. AC, adenylyl cyclase.

FIGURE 2

Signal amplification of the current responses. (a) Scheme of signal transduction cascade. cAMP is produced from caged cAMP by UV light photolysis. (b) Current amplification by double‐pulse stimulation in a single ORC. (c) Relationship between the 1st and 2nd response of the light‐induced current. Plots were fitted by Eq. 2 in C, which is based on the Hill equation (Eq. 1). (d) The dose‐response curve was drawn using the same protocol as in C. Arrows indicate the estimated [cAMP]i increased by the 1st light stimuli. (Takeuchi & Kurahashi, , Fig. 6d–f). (e) Local UV stimulation area (colored squares) along the single cilium. (f) Current response from F in e. (g) Current response from G in e. (h) Current response from H in e. (i) Current response from I in e. (j) Current response from J in e. (k) Current response from K in e. (l) Current response from the distance from the knob. (m) Superimposed from four different cilium data (Takeuchi & Kurahashi, , Fig. 5a‐i).

FIGURE 3

Olfactory adaptation. (a) Double‐pulse odorant stimulation and current response. Time course of adaptation and recovery. (b) Superimposition of the second response. Inter‐stimulus interval times are different, whereas stimulus intensities are the same. (c) Dose–response relationship showing a dynamic shift (Kurahashi & Menini, , figure 1a, c, d).

FIGURE 4

Diffusion limitation in the cilium. (a) Double‐light pulse stimulation. Left: Double‐pulse stimulation points. Right: Current response (Takeuchi & Kurahashi, , figure 5a‐h). (b) Distance between two stimulus points and the slope of the dose–response relationship. A decrease in slope angle indicates adaptation from calcium ion transfer, whereas an increase in slope angle indicates addition resulting from cAMP transfer. Eventually, the slope angle reaches zero within a few μm. (Takeuchi & Kurahashi, , figure 5j) (c) Simulation of the molecules in the tiny structure (Takeuchi & Kurahashi, , figure 9–11a‐h). (d) Scheme of simultaneously measurements channel current and Fluo4 fluorescent. (e) Photograph of the single ORC. White box shows scan area. (f) UV stimulation area in white box in e. (g) Superimposition of the current response and fluorescence intensity for the double‐pulse stimulus (Takeuchi & Kurahashi, , figure 6h).

FIGURE 5

Olfactory masking. (a) Three deodorizing approaches and a new concept: Olfactory masking. (b) Current suppression by TCA and suppressors. (Takeuchi et al., , figure 2a‐c). (c) Dose‐suppression relation in b. (Takeuchi et al., , figure 2d). (d) Current suppression by TCA and TCPT. (Takeuchi et al., 2013, figure 6a, b). (e) Dose‐suppression relationship among suppressors in d. (Takeuchi et al., , figure 6c). (f) Relationship between LogD (pH7.4) and half‐suppression concentration (Takeuchi et al., , figure 6d).