Mechanism of odorant adaptation in the olfactory receptor cell

Adaptation to odorants begins at the level of sensory receptor cells1–5, presumably through modulation of their transduction machinery. The olfactory signal transduction involves the activation of the adenylyl cyclase/cyclic AMP second messenger system which leads to the sequential opening of cAMP-gated channels and Ca2+ -activated chloride ion channels4–7. Several reports of results obtained from in vitro preparations describe the possible molecular mechanisms involved in odorant adaptation; namely, ordorant receptor phosphorylation8,9, activation of phosphodiesterase10, and ion channel regulation11–14. However, it is still unknown whether these putative mechanisms work in the intact olfactory receptor cell. Here we investigate the nature of the adaptational mechanism in intact olfactory cells by using a combination of odorant stimulation and caged cAMP photolysis15 which produces current responses that bypass the early stages of signal transduction (involving the receptor, G protein and adenylyl cyclase). Odorant- and cAMP-induced responses showed the same adaptation in a Ca2+ -dependent manner, indicating that adaptation occurs entirely downstream of the cyclase. Moreover, we show that phosphodiesterase activity remains constant during adaptation and that an affinity change of the cAMP-gated channel for ligands accounts well for our results. We conclude that the principal mechanism underlying odorant adaptation is actually a modulation of the cAMP-gated channel by Ca2+ feedback.