Interplay of Signaling Molecules in Olfactory Sensory Neuron toward Signal Amplification / 한양의대학술지

ABSTRACT

Over the last decades, piles of data have been accumulated to understand the olfactory sensation in every aspect, ranging from the intracellular signaling to cognitive perception. This review focuses on the ion conduction through multiple ion channels expressed in olfactory sensory neurons (OSNs) to describe how odorant binding to olfactory receptors is transduced into an electrical signal. Olfactory signal transduction and the generation of the depolarizing receptor current occur in the cilia, where the unique extraciliary environment of the nasal mucosa assists in the neuronal activation. Upon contacting with odorants, OSNs dissociate G protein-coupled receptors, initiating a signal transduction pathway that leads to firing of action potential. This signaling pathway has a unique, two step organization a cAMP-gated Ca2+ (CNG) channel and a Ca2+-activated Cl- channel (CACC), both of which contribute to signal amplification. This transduction mechanism requires an outward-directed driving force of Cl- established by active accumulation of Cl- within the lumen of the sensory cilia. To permit Cl- accumulation, OSNs avoid the expression of the 'Chloride Sensor WNK3', that functions as the main Cl- exclusion co-transporter in neurons of the central nervous system (CNS). Cl- accumulation provides OSNs with the driving force for the depolarization, increasing the excitatory response magnitude. This is an interesting adaptation because of the fact that the olfactory cilia reside in the mucus, outside the body, where the concentrations of ions are not as well regulated as they are in normal interstitial compartments.