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Current response and fluorescence intensity under scan mode. (A) Scheme of olfactory transduction and experimental procedures. (B) Photomicrograph of a single ORC. The white square shows the ROI area where UV stimulation was applied (stimulus ROI). Fluo-4 fluorescence was obtained from a much larger area in the experiment, but only data from the UV stimulus region are illustrated. (C) The current response to UV stimulation. The downward deflection of the upper trace indicates the period of UV stimulation. Duration: 2.22 s. This value represents the time needed for the raster scan of the ROI area. The actual UV application to the cilium comprises repetitive steps (Takeuchi and Kurahashi, 2008). (D) Fluorescence images. Left, before UV application; middle, during UV application; right, after UV application. Scaling Y, 0.09 µm. Scan speed, 2.22 s/scan. The intervals between image scan initiations were 7.04 s. Line sum, 4. Note that the increase in fluorescence is not obvious at the beginning of irradiation but becomes more noticeable in the lower region of the middle image. Three images correspond to the second, third, and fourth data points in F. (E) Positions of five analysis ROIs (red circles, 0.23 µm in diameter) used for fluorescence measurements. (F) Change in ΔF/F0. Plots were obtained from the five analysis ROIs indicated in E. Error bars show the SD from those data. Credit: Journal of General Physiology (2023). DOI: 10.1085/jgp.202213165

Researchers from Osaka University found that Ca2+ signaling simultaneously performed signal amplification and olfactory adaptation. The results demonstrated that this mysterious phenomenon was segregated inside the cilium. A novel system was used to observe changes in Ca2+ dynamics inside the thin structure of a cilium. Unveiling the mystery of Ca2+ signaling segregation further clarifies the mechanisms underlying the human sense of smell.

In a study published this month in the Journal of General Physiology, researchers revealed that the amplification and reduction of the sensory signal are both regulated by Ca2+, and the processes are clearly segregated within a tiny structure of a sensory cell.

The initial event that induces the sense of smell is the binding of odorant molecules to the hair-like structures, cilia, attached to the olfactory receptor neurons in the nose. This binding triggers the flow of ions causing an electrical excitation in the cilia, controlled by ion channels that promote the influx of extracellular positive ions into the semifluid compartment of the cilia.

As a result, the Ca2+ signal simultaneously performs the opposing effects of excitation and adaptation to regulate the activity of ion channels on the cilia. A series of events leading to the initiation of a biochemical cascade promotes the increase of Ca2+ inside the cilia: the current increases, impulses are generated, and information is sent to the brain to identify the scent. In the adaptation process, negative feedback signaling occurs to prevent saturation of ion channel activities and to adjust sensitivity to stimulus intensities.

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Direct comparison of time courses for membrane current and Ca2+ signal in the same location of the cilium. Credit: Hiroko Takeuchi and Takashi Kurahashi, Journal of General Physiology

“How the same ion controls both the increase and decrease in local current has been a mystery,” explains lead author Hiroko Takeuchi. “In this research, we aimed to determine whether the process of signal amplification and reduction is indeed segregated only inside the cilia.” The phenomenon remains a mystery because of the technical difficulty in observing the change in Ca2+ dynamics inside the thin structure of the cilia.


The researchers used a novel system to record channel activity and Ca2+ signaling simultaneously. The system applied four techniques: (1) visualization of Ca2+ dynamics in real-time using a Ca2+-sensitive dye, (2) measurement of current across the ciliary membrane (via ion channels), (3) UV activation of ion channels (through a photo-released substance) and (4) employment of confined laser beams for both the stimulation and imaging of the local cilium.


UV excitation of the local cilium immediately generated the inward current and Ca2+ signal; however, after the termination of the stimulus, the current decreased together with the reduction of Ca2+ signal. Surprisingly, however, the adaptation persisted for longer periods even after the Ca2+ signal disappeared. It seems likely that Ca2+ is kept bound exclusively to proteins that regulate the adaptation. “Our results were promising; these opposing effects of Ca2+ occurred separately by molecular kinetics in a tiny space of the native cilium,” says senior author Takashi Kurahashi.

The successful capture of ion channel activity and Ca2+ dynamics within the cilia is a key step toward understanding the human sense of smell. By elucidating the intricacies of Ca2+ signaling, the human sense of smell could be enhanced through the development of olfactory sensors or adjustments to the chemical environment of the nose.

The article, “Segregation of Ca2+ signaling in olfactory signal transduction,” was published in the Journal of General Physiology.

More information: Hiroko Takeuchi et al, Segregation of Ca2+ signaling in olfactory signal transduction, Journal of General Physiology (2023). DOI: 10.1085/jgp.202213165

Journal information: Journal of General Physiology

Provided by Osaka University

Source: Researchers identify cellular mechanism that improves olfactory function