Olfactory transduction is thought to be initiated by the binding of odorants to specific receptor proteins in the cilia of olfactory receptor cells (reviewed in refs 1–3). The mechanism by which odorant binding could initiate membrane depolarization is unknown, but the recent discovery of an odorant-stimulated adenylate cyclase in purified olfactory cilia4,5 suggests that cyclic AMP may serve as an intracellular messenger for olfactory transduction. If so, then there might be a conductance in the ciliary plasma membrane which is controlled by cAMP. Here we report that excised patches of ciliary plasma membrane, obtained from dissociated receptor cells, contain a conductance which is gated directly by cAMP. This conductance resembles the cyclic GMP-gated conductance that mediates phototransduction in rod and cone outer segments6,7, but differs in that it is activated by both cAMP and cGMP. Our data provide a mechanistic basis by which an odorant-stimulated increase in cyclic nucleotide concentration could lead to an increase in membrane conductance and therefore, to membrane depolarization. These data suggest a remarkable similarity between the mechanisms of olfactory and visual transduction and indicate considerable conservation of sensory transduction mechanisms.

A cyclic nucleotide-gated conductance in olfactory receptor cilia

Combinatorial and Chemotopic Odorant Coding in the Zebrafish Olfactory Bulb Visualized by Optical Imaging

Molecular recognition has evolved from a science designed to understand biological systems into a much more diverse area of research. While work continues to elucidate "nature's tricks" with respect to intermolecular interactions, much attention has turned to the perspective that molecular recognition, by design, can lead to new technologies. Applications ranging from molecular sensing to information storage and even working molecular machines have been envisioned. This review will highlight a few historical hallmarks of molecular recognition oriented at studying the basic science of intermolecular interactions, but then detail recent advances in molecular recognition aimed towards applications in the field of molecular sensing. Rational design can be used to create synthetic receptors with a good deal of predictability and selectivity, and many signal transduction mechanisms exist for converting these receptors into sensors. This is the first topic discussed. The concept of "differential" or "generalized" sensing is then presented, where one uses an array of sensors that do not necessarily conform to the "lock and key" principle. This approach to sensing is inspired by the mammalian senses of taste and smell, which we briefly describe. To mimic senses of taste and smell, one is naturally led to the use of combinatorial libraries, a direction of research that has seen continued growth over the past few years. We summarize the current state of the art in synthetic combinatorial receptors/sensors, and then predict a future direction that the field of molecular recognition will possibly take. The review is not meant for the specialist, but instead for a general audience. It does not present a highly detailed analysis of each individual topic: synthetic receptors, sensors, olfaction/gustation, and combinatorial receptors/sensors. Instead, this review shows how all these fields complement each other and fit together to create sensing devices. Our conclusion is that specific analyte sensing, differential sensing, and combinatorial chemistry can and will be combined to create sensor arrays, and give the subfield of molecular recognition that uses synthetic systems a bright future in this type of sensing scenario.

Sensing A Paradigm Shift in the Field of Molecular Recognition: From Selective to Differential Receptors.

Schild, Detlev, and Diego Restrepo. Transduction Mechanisms in Vertebrate Olfactory Receptor Cells. Physiol. Rev. 78: 429–466, 1998. — Considerable progress has been made in the understanding of tr...

Transduction Mechanisms in Vertebrate Olfactory Receptor Cells

The odorant-sensitive adenylate cyclase of olfactory receptor cells. Differential stimulation by distinct classes of odorants.

The interaction of an odorant with the chemosensitive membrane of olfactory receptor neurons initiates a sequence of molecular and membrane events leading to sensory transduction, impulse initiation, and the transmission of sensory information to the brain. The main steps in this sequence are summarized in Figure 6. Several lines of evidence support the hypothesis that the initial molecular events and subsequent stages of transduction are mediated by odorant receptor sites and associated ion channels located in the membrane of the cilia and apical dendritic knob of the olfactory receptor neuron. Similarly, the membrane events associated with impulse initiation and propagation are mediated by voltage-gated channels located in the initial axonal segment and the axolemma. The ionic and electrical events associated with the proposed sequence have been characterized in general using a variety of experimental techniques. The identification, localization, and sequence of membrane events are consistent with the neurophysiological properties observed in specific regions of the bipolar receptor neuron. The influence of other cells in the primary olfactory pathway such as the sustentacular cells in the olfactory epithelium, the Schwann cells in the olfactory nerve, and the astrocytes in the olfactory nerve layer in the olfactory bulb on the physiological activity of the olfactory receptor neuron is an emerging area of research interests. The general principles derived from the experimental results described in this review provide only a framework that is both incomplete and of necessity somewhat speculative. As noted in the Introduction, the multidisciplinary study of the primary olfactory pathway is undergoing a renaissance of research interest. The application of modern biophysical, cell, and molecular biological techniques to the basic issues of odorant recognition and membrane excitability will clarify the speculations and lead to the establishment of new hypotheses. Three broad areas of research will benefit from such studies. First, the application of biophysical techniques will lead to a detailed characterization of the membrane properties and associated ion conductance mechanisms. Second, the isolation and biochemical characterization of intrinsic membrane and cytosolic proteins associated with odorant recognition, sensory transduction, and the subsequent electrical events will result from the utilization of cell and molecular biological techniques.(ABSTRACT TRUNCATED AT 400 WORDS)

Functional properties of vertebrate olfactory receptor neurons

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Functional properties of vertebrate olfactory receptor neurons