2ND-MESSENGER SIGNALING IN OLFACTORY TRANSDUCTION

Olfactory receptor neurons respond to odorants with G-protein mediated increases in the concentration of cyclic adenosine 3',5'-monophosphat e (cAMP) and / or inositol 1,4,5-trisphospahte (InsP(3)), These two se cond messengers directly regulate opening of cAMP- and InsP(3)-regulat ed conductances localized to the apical transduction compartments of t he cell (cilia and olfactory knob), In the presence of physiological c oncentrations of extracellular Ca2+, these second messenger regulated conductances mediate influx of Ca2+ into the olfactory neuron resultin g in large, localized increases in intracellular Ca2+ ([Ca2+](i)). A s ignificant advance in our understanding of the molecular mechanisms of olfaction is the recent realization that this increase in [Ca2+](i) p lays an important role as a ''third messenger'' in olfactory transduct ion, Second messenger dependent increases in [Ca2+](i) cause opening o f ciliary Ca2+-activated Cl-, cation and / or K+ channels that can car ry a large percentage of the generator current, thus amplifying the si gnal substantially, As a result of this sequence of events, the genera tor potential in olfactory neurons can be depolarizing, leading to exc itation of the neuron, or hyperpolarizing, leading to suppression of b asal action potential firing rate, This dual effect of odorants on olf actory neurons may play an important role in quality coding and in the ability to detect low concentrations of odorants, particularly in com plex mixtures. (C) 1996 John Wiley & Sons, Inc.