Mechanism of Signal Amplification in the Olfactory Sensory Cilia

Abstract

Molecular mechanisms underlying olfactory signal amplification were investigated by monitoring cAMP dynamics in the intact sensory cilia. We saw that [cAMP] i increased superlinearly with time during odorant stimuli for Ͼ1 s. This time course was remarkably different from that obtained with the rapid quench method previously applied to the in vitro preparation, in which [cAMP] i change has been reported to be transient. The superlinear increase of [cAMP] i was attributable to a gradual increase of cAMP production rate that was consistent with the thermodynamical interaction model between elemental molecules, as has been revealed on the rod photoreceptor cell. It thus seems likely that the fundamental mechanism for molecular interactions between olfactory transduction elements is similar to that of the rod. In olfaction, however, cAMP production was extremely small (ϳ200,000 molecules/s/cell at the maximum), in contrast to the cGMP hydrolysis in the rod (250,000 molecules/photon). The observed numbers indicate that the olfactory receptor cell has lower amplification at the enzymatic cascade. Seemingly, such low amplification is a disadvantage for the signal transduction, but this unique mechanism would be essential to reduce the loss of ATP that is broadly used for the activities of cells. Apparently, transduction by a smaller number of second-messenger formations would be achieved by the fine ciliary structure that has a high surface-volume ratio. In addition, it is speculated that this low amplification at their enzymatic processes may be the reason why the olfactory receptor cell has acquired high amplification at the final stage of transduction channels, using Ca 2ϩ as a third messenger.

Molecular components of signal amplification in olfactory sensory cilia

“…7, green), the odorinduced synthesis of cAMP, operates with low efficiency (30,31). A few μM cAMP is, however, sufficient to activate the cAMP-gated transduction channels.…”

Distribution, Amplification, and Summation of Cyclic Nucleotide Sensitivities within Single Olfactory Sensory Cilia

“…Olfactory receptor cells (ORCs) were dissociated enzymatically (0.1% collagenase) from the olfactory epithelium of the newt (Cynops pyrrhogaster) and mouse (Jcl:ICR, 6 weeks old or older) as described previously (Takeuchi and Kurahashi, 2005). The experiments were performed under the latest ethical guidelines for animal experimentation at Osaka University, which is based on international experimental regulations.…”

“…Ciliary currents were recorded with the whole-cell (WC) recording configuration (Hamill et al, 1981) under the voltage-clamp mode as described previously (Takeuchi and Kurahashi, 2005). Culture dish was mounted on the inverted microscope (Axiovert; Zeiss, Oberkochen, Germany).…”

Disynaptic Amplification of Metabotropic Glutamate Receptor 1 Responses in the Olfactory Bulb

“…However, olfactory neurons are intermittently exposed to variable concentrations of an odorant as the animal moves through the medium and turbulent air-flows carry odorant molecules. Furthermore, signal amplification does not seem to take place at the level of olfactory neurons because of the low efficacy with which olfactory receptors translate odorant binding into biochemical (Takeuchi and Kurahashi, 2005) and electrical (Bhandawat et al, 2005) signals. The high number of olfactory neurons expressing a given olfactory receptor may compensate for this low efficacy.…”