A B S T R A C T

Sensing smells of foods, prey, or predators determines animal survival. Olfactory sensory neurons in the olfactory

epithelium (OE) detect odorants, where cAMP and Ca2+play a significant role in transducing odorant inputs to

electrical activity. Here we show Anoctamin 9, a cation channel activated by cAMP/PKA pathway, is expressed in

the OE and amplifies olfactory signals. Ano9-deficient mice had reduced olfactory behavioral sensitivity, electro-

olfactogram signals, and neural activity in the olfactory bulb. In line with the difference in olfaction between

birds and other vertebrates, chick ANO9 failed to respond to odorants, whereas chick CNGA2, a major transduction

channel, showed greater responses to cAMP. Thus, we concluded that the signal amplification by ANO9

is important for mammalian olfactory transduction.