Receptor Mechanisms in Olfaction

Dionne, Vincent

Abstract

Odors are transduced by processes that modulate ion channels in the membranes of olfactory receptor neurons. This study is aimed at identifying and characterizing these processes with the long-range goal of learning how the olfactory system detects, discriminates, and encodes odor information. The studies will be conducted with Necturus maculosus, a neotenic salamander that has been a valuable animal model for physiological investigations. Its large cells and aquatic habitat make it especially well suited for studying odor transduction. While specific features of odor transduction may not be shared by all animals, the principles and essential features that can be learned from Necturus may be universal. Patch-clamp electrophysiological methods, flash photolysis of caged compounds, calcium imaging, and molecular biological techniques will be used to address several long-standing questions about odor transduction. These include the characterization of a chloride channel that appears to be directly gated by intracellular cyclic AMP and cyclic GMP. This conductance, first detected in our studies, has a novel dependence on cyclic nucleotides that suggests it may be involved in odor transduction. A separate study will examine an odor transduction pathway that is stimulated by amino acids and involves the elevation of intracellular calcium in olfactory receptor neurons. The third part of the study focusses on the olfactory receptor gene family. In preliminary studies, we have cloned six olfactory receptor genes from Necturus.. Surprisingly in light of this animal's aquatic habitat, five of the six genes appear to be mammal-like while only one is fish-like. Using molecular methods, these and additional members of the olfactory receptor gene family will be studied-to learn about their functions in olfactory receptor neurons.