SELECTIVITY AND RESPONSE CHARACTERISTICS OF HUMAN OLFACTORY NEURONS

Transduction mechanisms were investigated in human olfactory neurons b y determining characteristics of odorant-induced changes in intracellu lar calcium concentration ([Ca2+](1)). Olfactory neurons were freshly isolated from nasal biopsies, allowed to attach to coverslips, and loa ded with the calcium-sensitive indicator fura-2. Changes in [Ca2+](i) were studied in response to exposure to individual odors, or odorant m ixtures composed to distinguish between transduction pathways mediated by adenosine 3'5'-monophosphate (cAMP; mix A) or inositol 1,4,5-trisp hosphate (InsP(3); mix B). Overall, 52% of biopsies produced one or mo re odorant-responsive olfactory neurons, whereas 24% of all olfactory neurons tested responded to odorant exposure with a change in [Ca2+](i ). As in olfactory neurons from other species, the data suggest that o dorant exposure elicited calcium influx via second-messenger pathways involving cAMP or InsP(3). Unlike olfactory neurons from other species that have been tested, some human olfactory neurons responded to odor ants with decreases in [Ca2+](i). Also in contrast with olfactory neur ons from other species, human olfactory neurons were better able to di scriminate between odorant mixtures in that no neuron responded to mor e than one type of odor or mixture. These results suggest the presence of a previously unreported type of olfactory transduction mechanism, and raise the possibility that coding of odor qualities in humans may be accomplished to some degree differently than in other vertebrates, with the olfactory neuron itself making a greater contribution to the discrimination process.