Segregation of Ca(2+) signaling in olfactory signal transduction

Olfactory signal transduction is conducted through a cAMP-mediated second messenger cascade. The cytoplasmic Ca(2+) 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 Ca(2+)-activated Cl(−) channel whereas adaptation is regulated by Ca(2+) feedback to the CNG channel. Thus, the influx of Ca(2+) and the resultant increase in cytoplasmic Ca(2+) 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. Ca(2+) 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 Ca(2+) imaging, we found that free Ca(2+) in the local ciliary cytoplasm decreased along with a reduction in the current containing Ca(2+)-activated Cl(−) components returning to the basal level, whereas Ca(2+)-dependent adaptation persisted for a longer period. The activity of Cl(−) channels is highly likely to be regulated by the free Ca(2+) that is present only immediately after the influx through the CNG channel, and an exclusive interaction between Ca(2+) and Ca(2+)-binding proteins that mediate the adaptation may modulate the adaptation lifetime.