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The Neurobiology of olfaction
The common belief is that human smell perception is much reduced compared with other mammals, so that whatever abilities are uncovered and investigated in animal research would have little significance for humans. However, new evidence from a variety of sources indicates this traditional view is likely overly simplistic.
The Neurobiology of Olfaction provides a thorough analysis of the state-of-the-science in olfactory knowledge and research, reflecting the growing interest in the field. Authors from some of the most respected laboratories in the world explore various aspects of olfaction, including genetics, behavior, olfactory systems, odorant receptors, odor coding, and cortical activity.
Until recently, almost all animal research in olfaction was carried out on orthonasal olfaction (inhalation). It is only in recent years, especially in human flavor research, that evidence has begun to be obtained regarding the importance of retronasal olfaction (exhalation). These studies are beginning to demonstrate that retronasal smell plays a large role to play in human behavior.
Highlighting common principles among various species – including humans, insects, Xenopus laevis (African frog), and Caenorhabditis elegans (nematodes) – this highly interdisciplinary book contains chapters about the most recent discoveries in odor coding from the olfactory epithelium to cortical centers. It also covers neurogenesis in the olfactory epithelium and olfactory bulb. Each subject-specific chapter is written by a top researcher in the field and provides an extensive list of reviews and original articles for students and scientists interested in further readings
Cyclic nucleotide-gated channels in visual and olfactory transduction
Rod and cone photoreceptors are the light detectors in the visual system whereas olfactory receptor cells are the odorant detectors in the olfactory system. Despite the two very different types of stimuli, light in photoreceptors, and odorant molecules in olfactory receptor cells, the mechanisms of visual and olfactory transduction appear to have many homologies. Both stimuli trigger a chain of enzymatic events that terminates in a change in the concentration of a cyclic nucleotide: a decrease in the concentration of cGMP in photoreceptors, and an increase in the concentration of cAMP in olfactory receptor cells. These cyclic nucleotides directly gate cation channels and therefore a change in their concentration induced by the external stimulus is converted into an electrical signal. The analysis of the ionic selectivity properties of cyclic nucleotidegated channels in retinal rods, cones and in olfactory receptor cells shows that there are many similarities between these channels. They do not appreciably select between alkali monovalent cations and can be permeated and blocked by divalent cations. Their ionic permeation properties are consistent with the presence of a cation-binding site of high-field strength in the pore. © 1995
Calcium signalling and regulation in olfactory neurons
The odorant-induced Ca2+ increase inside the cilia of vertebrate olfactory sensory neurons controls both excitation and adaptation. The increase in the internal concentration of Ca2+ in the cilia has recently been visualized directly and has been attributed to Ca2+ entry through cAMP-gated channels. These recent results have made it possible to further characterize Ca2+'s activities in olfactory neurons. Ca2+ exerts its excitatory role by directly activating Cl-channels. Given the unusually high concentration of ciliary Cl-, Ca2+'s activation of Cl- channels causes an efflux of Cl-from the cilia, contributing high-gain and low-noise amplification to the olfactory neuron depolarization, Moreover, in combination with calmodulin, Ca2+ mediates odorant adaptation by desensitizing cAM P-gated channels. The restoration of the Ca2+ concentration to basal levels occurs via a Na+/Ca2+ exchanger, which extrudes Ca2+ from the olfactory cilia
Currents carried by monovalent cations through cyclic GMP-activated channels in excised patches from salamander rods.
The blocking effect of l-cis-diltiazem on the light-sensitive current of isolated rods of the tiger salamander.
The effect of the organic compound l-cis-diltiazem on the light-sensitive current of isolated rods of the tiger salamander was analysed by rapidly changing the extracellular medium using the method of Hodgkin et al. (1985). Addition to the extracellular medium of small amounts of l-cis-diltiazem rapidly inhibits the photocurrent. Complete suppression of the current was observed with 1 m M l-cis-diltiazem. Half blockage of the photocurrent occurred with about 150 μM l-cis-diltiazem. The blocking effect of l-cis-diltiazem was enhanced by light and by a reduction of extracellular Na. A concentration of l-cis-diltiazem of 140 μM, which suppresses one third of the photocurrent, was able to completely suppress the photocurrent carried by Ba. It is suggested that l-cis-diltiazem blocks the light-sensitive channel, possibly competing with cyclic guanosine-3′-5′-monophosphate (cGMP) for an internal regulatory site
The effect of cadmium on the light-sensitive current in isolated rods of the tiger salamander.
The effect of cadmium on the light-sensitive current of isolated rods of the tiger salamander was analysed by rapidly changing the ionic medium using the technique of Hodgkin et al. (1985). Addition of millimolar amounts of cadmium to the extracellular medium caused a rapid, but transient, decrease of the photocurrent. The effect of cadmium on the movement of divalent cations, such as Ba2+ and Ca2+, differs according to the experimental protocol: when cadmium is introduced into the bathing medium at the same time as Ca2+ or Ba2+, it blocks the entry of these ions into the rod; and when the rod is exposed to cadmium first for a few seconds the entry of Ca2+ and Ba2+ is enhanced. The effect of cadmium is best explained as a dual effect: firstly, an external effect on the channel, and secondly, by metabolic changes, which are caused by a drop of intracellular Ca2+
The permeability of the cGMP-activated channel to organic cations in retinal rods of the tiger salamander
1. The permeability of the channel activated by guanosine 3',5'‐cyclic monophosphate (cGMP) to many organic monovalent cations was determined by recording macroscopic currents in excised inside‐out patches of plasma membrane from isolated retinal rod outer segments of the tiger salamander. 2. Current‐voltage relations were measured when the NaCl of the bathing medium was replaced by salts of organic cations. Permeability ratios relative to Na+ ions were calculated with the Goldman‐Hodgkin‐Katz potential equation from the measured changes of reversal potentials. 3. Hydroxylammonium+, hydrazinium+ and methylammonium+, which are molecules of very similar shape and size, permeate the channel with very different permeability ratios: 5.92, 1.99 and 0.60 respectively. 4. Methylated and ethylated ammonium+ compounds were investigated. It was found that, not only methylammonium+, but also dimethylammonium+ and ethylammonium+ were permeant with permeability ratios of 0.6, 0.14 and 0.16 respectively. Trimethylammonium+, tetramethylammonium+, diethylammonium+, triethylammonium+, and tetraethylammonium+ were not permeant. 5. Guanidinium+ and its derivatives formamidinium+, aminoguanidinium+, acetamidinium+ and methylguanidinium+ were all permeant with permeability ratios 1.12, 1.00, 0.63, 0.36 and 0.33 respectively. 6. The cGMP‐activated channel was found to be permeable to at least thirteen organic cations. Molecular models of the permeant cations indicate that the cross‐section of the narrowest part of the pore must be at least as large as a rectangle of 0.38 x 0.5 nm dimensions
Effects of calcium on the gramicidin A single channel in phosphatidylserine membranes: screening and blocking.
In phosphatidylserine membranes the decrease in the conductance of the gramicidin A single channel caused by calcium is attributed to a reduction of surface potential and to a direct blocking of the pore (Apell et al. 1979). The aim of this paper is to make a quantitative evaluation of these two effects. We recorded the conductance of gramicidin single channels in 100 mM KCl in the presence of different amounts of CaCl2, MgCl2 or TEACl. The ionic activities at the channel mouth were calculated using the Gouy-Chapman-Stern theory. Our experiments showed that even when the K+ activity at the channel mouth was estimated to be the same, the single channel conductance was lower if divalent cations were present. This effect is attributed to a blocking action of these ions
Developmental expression of the calcium-activated chloride channels TMEM16A and TMEM16B in the mouse olfactory epithelium
Calcium-activated chloride channels are involved in several physiological processes including olfactory perception. TMEM16A and TMEM16B, members of the transmembrane protein 16 family (TMEM16), are responsible for calcium-activated chloride currents in several cells. Both are present in the olfactory epithelium of adult mice, but little is known about their expression during embryonic development. Using immunohistochemistry we studied their expression in the mouse olfactory epithelium at various stages of prenatal development from embryonic day (E) 12.5 to E18.5 as well as in postnatal mice. At E12.5, TMEM16A immunoreactivity was present at the apical surface of the entire olfactory epithelium, but from E16.5 became restricted to a region near the transition zone with the respiratory epithelium, where localized at the apical part of supporting cells and in their microvilli. In contrast, TMEM16B immunoreactivity was present at E14.5 at the apical surface of the entire olfactory epithelium, increased in subsequent days, and localized to the cilia of mature olfactory sensory neurons. These data suggest different functional roles for TMEM16A and TMEM16B in the developing as well as in the postnatal olfactory epithelium. The presence of TMEM16A at the apical part and in microvilli of supporting cells is consistent with a role in the regulation of the chloride ionic composition of the mucus covering the apical surface of the olfactory epithelium, whereas the localization of TMEM16B to the cilia of mature olfactory sensory neurons is consistent with a role in olfactory signal transduction
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