NONLINEAR AMPLIFICATION BY CALCIUM-DEPENDENT CHLORIDE CHANNELS IN OLFACTORY RECEPTOR-CELLS

THE sense of smell is highly evolved in mammals, allowing discriminati on between a vast number of odorants, with detection thresholds as low as 10(-17) M (ref. 1). Although several features of mammalian olfacto ry transduction have been revealed by biochemical and molecular biolog ical studies2-11, the odorant-induced membrane current has remained el usive. In amphibians this current is mediated by cyclic-nucleotide-gat ed channels12-15, which depolarize the cell by Na+ and Ca+ influx16,17 and consequent Cl- efflux through Ca2+-dependent Cl- channels18,19. T he Cl- current may be absent in mammals, however, because its proposed role is linked to the aquatic habitat of amphibians18. Here we show t hat the transduction current in rat olfactory receptor cells is initia ted by cyclic-nucleotide-gated channels. The Cl- current is also prese nt and endows the transduction current with a steep sigmoidal dependen ce on cyclic AMP concentration in both rat and in an amphibian, indica ting a new function for the Cl- channel: nonlinear amplification of th e transduction signal, whereby suprathreshold responses are boosted re lative to basal transduction noise.