Molecular mechanisms of olfactory transduction. The binding of odorant molecules to an odor-ant receptor (OR) induces the G-protein-mediated activation of adenylyl cyclase. cAMP directly gates CNG channels, generating a depolarizing influx of Na⁺ and Ca²⁺. The increase in intraciliary Ca²⁺ mediates both excitatory and inhibitory events. Ca²⁺ gates a CI⁻ channel that produces a depolarizing efflux of CI⁻ (Cl-Ca). On the other hand, Ca²⁺, through calmodulin (CaM) and/or other Ca²⁺-binding proteins, mediates the reduction of cAMP sensitivity of CNG channels and activates the PDE that hydrolyzes cAMP to AMP. Intraciliary Ca²⁺ concentration returns to basal level through the activity of a Na⁺/Ca²⁺-exchanger and Ca²⁺-ATPase.