Mechanism of the excitatory Cl- response in mouse olfactory receptor neurons

In vertebrate olfactory receptor neurons (ORNs), the odorant-triggered receptor current flows through two distinct ion channels on the sensory cilia: Ca2+ influx through a cyclic nucleotide-gated (CNG) channel followed by CI- efflux through a Ca2+-activated anion channel. The excitatory CI- current amplifies the small CNG current and crucially depends on a high intracellular CI- concentration. We show here that a Na+-K+-2CI(-) cotransporter, NKCC1, is required for this CI- current, in that ORNs deficient in NKCC1 or incubated with an NKCC blocker (bumetanide) lack the CI- current. Surprisingly, immunocytochemistry indicates that NKCC1 is located on the somata and dendrites of ORNs rather than the cilia, where transduction occurs. This topography is remarkably similar to the situation in secretory epithelial cells, where basolateral CI- uptake and apical CI- efflux facilitate transepithelial fluid movement. Thus, a single functional architecture serves two entirely different purposes, probably underscoring the epithelial origin of the ORNs.