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Activation of most primary sensory neurons results in transduction currentsthat are carried by cations. One notable exception is the vertebrate olfactoryreceptor neuron (ORN), where the transduction current is carried largely by theanion $Cl^-$. However, it remains unclear why ORNs use an anionic current forsignal amplification. We have sought to provide clarification on this topic bystudying the so far neglected dynamics of $Na^+$, $Ca^{2+}$, $K^+$ and $Cl^-$in the small space of olfactory cilia during an odorant response. Usingcomputational modeling and simulations we compared the outcomes of signalamplification based on either $Cl^-$ or $Na^+$ currents. We found thatamplification produced by $Na^+$ influx instead of a $Cl^-$ efflux isproblematic due to several reasons: First, the $Na^+$ current amplitude variesgreatly depending on mucosal ion concentration changes. Second, a $Na^+$current leads to a large increase in the ciliary $Na^+$ concentration during anodorant response. This increase inhibits and even reverses $Ca^{2+}$ clearanceby $Na^+/Ca^{2+}/K^+$ exchange, which is essential for response termination.Finally, a $Na^+$ current increases the ciliary osmotic pressure, which couldcause swelling to damage the cilia. By contrast, a transduction pathway basedon $Cl^-$ efflux circumvents these problems and renders the odorant responserobust and reliable.

The $Ca^{2+}$-activated $Cl^-$ current ensures robust and reliable signal amplification in vertebrate olfactory receptor neurons