Mechanism of odorant adaptation in the olfactory receptor cell

Abstract

Adaptation to odorants begins at the level of sensory receptor cells^1–5, 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 channels^4–7. Several reports of results obtained from in vitro preparations describe the possible molecular mechanisms involved in odorant adaptation; namely, ordorant receptor phosphorylation^8,9, activation of phosphodiesterase¹⁰, and ion channel regulation^11–14. 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.