Cyclic-nucleotide-gated cation current and Ca²⁺-activated Cl current elicited by odorant in vertebrate olfactory receptor neurons

Olfactory transduction in vertebrate olfactory receptor neurons (ORNs) involves primarily a cAMP-signaling cascade that leads to the opening of cyclic-nucleotide-gated (CNG), nonselective cation channels. The consequent Ca²⁺ influx triggers adaptation but also signal amplification, the latter by opening a Ca²⁺-activated Cl channel (ANO2) to elicit, unusually, an inward Cl current. Hence the olfactory response has inward CNG and Cl components that are in rapid succession and not easily separable. We report here success in quantitatively separating these two currents with respect to amplitude and time course over a broad range of odorant strengths. Importantly, we found that the Cl current is the predominant component throughout the olfactory dose-response relation, down to the threshold of signaling to the brain. This observation is very surprising given a recent report by others that the olfactory-signal amplification effected by the Ca²⁺-activated Cl current does not influence the behavioral olfactory threshold in mice.