Olfactory response termination involves Ca-ATPase in vertebrate olfactory receptor neuron cilia

Olfactory transduction takes place in the cilia of olfactory receptor neurons (ORNs) (for review see Kleene, 2008). The process begins with the activation of an odorant receptor in the ciliary membrane, followed by synthesis of cAMP through activation of adenylyl cyclase (Lowe et al., 1989) via a G protein–coupled cascade. The ensuing increase in cAMP concentration causes CNG channels to open (Nakamura and Gold, 1987; Zufall et al., 1994), leading to an increase in intraciliary Ca concentration (Leinders-Zufall et al., 1997) and depolarization of the cell membrane. When the Ca concentration rises, it opens a Ca-activated Cl conductance (Kleene and Gesteland, 1991), enabling Cl efflux from the cilia, which greatly amplifies the small Ca current flowing through the CNG channels and further depolarizes the ORN (Kurahashi and Yau, 1993; Lowe and Gold, 1993). Termination of the response to odor requires not only deactivation of the transduction cascade and closure of the CNG channels, but also cessation of Cl efflux through the Ca-activated Cl conductance. In frog and mouse ORNs, closure of the Ca-activated Cl conductance, which contributes 70–90% of the total odorinduced current, depends directly on the restoration of the intraciliary Ca concentration to pre-stimulus levels