Segregation of Ca2+ signaling in olfactory signal transduction

In olfactory transduction, Ca2+ signaling is used for two opposing functions, namely signal boosting and signal reduction through adaptation, which could be interpreted to compensate for each other. Here, however, we show that these functions are clearly segregated by molecular dynamics. Olfactory signal transduction is conducted through a cAMP-mediated second messenger cascade. The cytoplasmic Ca2+ concentration increases through the opening of CNG channels, a phenomenon that underlies two major functions, namely, signal boosting and olfactory adaptation. Signal boosting is achieved by an additional opening of the Ca2+-activated Cl- channel whereas adaptation is regulated by Ca2+ feedback to the CNG channel. Thus, the influx of Ca2+ and the resultant increase in cytoplasmic Ca2+ levels play seemingly opposing effects: increasing the current while reducing the current through adaptation. The two functions could be interpreted as compensating for each other. However, in real cells, both functions should be segregated. Ca2+ dynamics in olfactory cilia need to be directly measured, but technical difficulties accompanying the thin structure of olfactory cilia have prevented systematic analyses. In this study, using a combination of electrophysiology, local photolysis of caged cAMP, and Ca2+ imaging, we found that free Ca2+ in the local ciliary cytoplasm decreased along with a reduction in the current containing Ca2+-activated Cl- components returning to the basal level, whereas Ca2+-dependent adaptation persisted for a longer period. The activity of Cl- channels is highly likely to be regulated by the free Ca2+ that is present only immediately after the influx through the CNG channel, and an exclusive interaction between Ca2+ and Ca2+-binding proteins that mediate the adaptation may modulate the adaptation lifetime.