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ScienceWeek
CELL BIOLOGY: ON TRP CHANNELS
The following points are made by David E. Clapham (Nature 2003 426:517):
1) The human genome encodes hundreds of channels that broker the passage of charged ions across impermeable lipid bilayers(1). While energy-requiring pumps labor to build charge and concentration gradients across the membrane, ion channels spend this stored energy, much as a switch releases the electrical energy of a battery. Small conformational changes cause channels to open, allowing over ten million ions to flow per second through each channel. Ca2+ ions are particularly important in cellular homeostasis and activity, and the surface of each cell holds thousands of channels that precisely control the timing and entry of Ca2+ ions.
2) Transient receptor potential (TRP) channels were first described in Drosophila, where photoreceptors carrying trp gene mutations exhibited a transient voltage response to continuous light(2,3). Unlike most ion channels, TRP channels are identified by their homology rather than by ligand function or selectivity, because their functions are disparate and often unknown. They have been called "store-operated channels" (SOCs), but this description is theoretical and related to a poorly understood phenomenon.
3) The known functions are diverse. Yeast use a TRP channel to perceive and respond to hypertonicity(4,5). Nematodes use TRP channels at the tips of neuronal dendrites in their "noses" to detect and avoid noxious chemicals. Male mice use a pheromone-sensing TRP channel to tell males from females. Humans use TRP channels to appreciate sweet, bitter and umami (amino acid) tastes, and to discriminate warmth, heat and cold. In each of these cases, TRPs mediate sensory transduction, not only in a classical sense, for the entire multicellular organism, but also at the level of single cells. Almost all mammalian TRP channel genes are now known.
4) Mammalian TRP channels comprise six related protein families with sequence identity as low as 20%. All TRP channels are putative six-transmembrane (6TM) polypeptide subunits that assemble as tetramers to form cation-permeable pores. In general, they are almost ubiquitously expressed and most have splice variants. So most cells have a number of TRP channel proteins.
5) In summary: TRP channels are the vanguard of our sensory systems, responding to temperature, touch, pain, osmolarity, pheromones, taste and other stimuli. But their role is much broader than classical sensory transduction. They are an ancient sensory apparatus for the cell, not just the multicellular organism, and they have been adapted to respond to all manner of stimuli, from both within and outside the cell.
References (abridged):
1. Hille, B. Ion Channels of Excitable Membranes 3rd edn, 663-723 (Sinauer, Sunderland, MA, 2001)
2. Minke, B. Drosophila mutant with a transducer defect. Biophys. Struct. Mech. 3, 59-64 (1977)
3. Montell, C., Jones, K., Hafen, E. & Rubin, G. Rescue of the Drosophila phototransduction mutation trp by germline transformation. Science 230, 1040-1043 (1985)
4. Denis, V. & Cyert, M. S. Internal Ca2+ release in yeast is triggered by hypertonic shock and mediated by a TRP channel homologue. J. Cell Biol. 156, 29-34 (2002)
5. Zhou, X. L. et al. The transient receptor potential channel on the yeast vacuole is mechanosensitive. Proc. Natl Acad. Sci. USA 100, 7105-7110 (2003)
Nature http://www.nature.com/nature
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RECEPTORS AND TRANSDUCTION IN TASTE
The following points are made by Bernd Lindemann (Nature 2001 413:219):
1) There is no life form known between bacteria and mammals that would neglect to check its intake of matter by chemoreceptive scrutiny. A human baby, only a few days old, already can distinguish sweet and bitter and express pleasure for sweet taste but displeasure for bitter taste(1). Inorganic ions, sugars and polysaccharides, amino acids and peptides, toxins and "xenobiotics" are all subject to nutritional chemoreception followed by adaptive behavior. But details differ widely, depending on the complexity of the organism and the ecological niche that it occupies. Even in closely related species, distinct differences in sensory performance may be noted, which seem to match the nutritional "needs" of a species. To understand how such a match arose, that is, how receptor specificity changed with the availability of food ingredients, is perhaps the most fascinating of the future tasks of taste research.
2) Already in worms, like the model nematode Caenorhabditis elegans, a distinction can be made between olfaction and taste(2). These two chemoreceptive senses are more clearly separate in arthropods and they are quite distinct in vertebrates. In the fruit fly Drosophila melanogaster, for example, taste sensations are mediated by nerve cells of characteristic topology. Their sensory dendrites are contained in "hairs" found on the body surface. Other taste neurons, found on the labellum and clustered around the pharynx, express a family of G-protein-coupled receptors (GPCRs) named GR3. This family, however, contains candidate receptors for both taste and olfaction, as its genes are expressed in both gustatory and olfactory primary neurons(4). In contrast, the taste receptor cells of vertebrates are not neurons, but originate from the epithelial covering of the body(5).
3) Vertebrate taste cells are small bipolar cells. To connect to the oral space, they send a thin dendritic process to the epithelial surface. The cells occur either singly or densely packed in taste buds, where up to 100 form a functional unit. Although taste buds also occur abundantly on the body surface and barbels of some fish, all vertebrates have taste buds in the oral epithelium, typically on tongue, palate and pharynx. On the tongue, the taste buds are mounted in special folds and protrusions called papillae. The marker molecule gustducin, a taste-specific G protein, shows additional "taste cells" in the nasal mucosa and in the stomach.
4) In summary: Taste is the sensory system devoted primarily to a quality check of food to be ingested. Although aided by smell and visual inspection, the final recognition and selection relies on chemoreceptive events in the mouth. Emotional states of acute pleasure or displeasure guide the selection and contribute much to our quality of life. Membrane proteins that serve as receptors for the transduction of taste have for a long time remained elusive. But screening the mass of genome sequence data that have recently become available has provided a new means to identify key receptors for bitter and sweet taste. Molecular biology has also identified receptors for salty, sour and umami (L-glutamate) taste.
References (abridged):
1. Ganchrow, J. R., Steiner, J. E. & Daher, M. Neonatal facial expressions in response to different qualities and intensities of gustatory stimuli. Infant Behav. Dev. 6, 189-200 (1983)
2. Pierce-Shimomura, J. T., Faumont, S., Gaston, M. R., Pearson, B. J. & Lockery, S. R. The homeobox gene lim-6 is required for distinct chemosensory representations in C. elegans. Nature 410, 694-698 (2001)
3. Clyne, P. J., Warr, C. G. & Carlson, J. R. Candidate taste receptors in Drosophila. Science 287, 1830-1834 (2000)
4. Scott, K. et al. A chemosensory gene family encoding candidate gustatory and olfactory receptors in Drosophila. Cell 104, 661-673 (2001)
5. Stone, L. M., Finger, T. E., Tam, P. P. & Tan, S. S. Taste receptor cells arise from local epithelium, not neurogenic ectoderm. Proc. Natl Acad. Sci. USA 92, 1916-1920 (1995)
Nature http://www.nature.com/nature
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ON THE CHEMISTRY AND BIOLOGY OF TASTE
The following points are made by H.M. Rouhi (Chem. Eng. News 2001 10 Sep):
1) Taste is currently the least understood of the human senses. Unlike vision, audition, or olfaction, taste is an area of neuroscience in which fundamental questions have not yet been fully answered because the biological system is difficult to study. Among the basic questions awaiting answers are how various tastes are detected and how the brain processes the information and knows what the mouth has tasted.
2) Adding to the complexity is the fact that taste cells are apparently not static, but are continually being produced and discarded, with the nervous system continually making new connections to new taste cells. Understanding the mechanisms of taste perception has far-reaching implications for various industries; in addition, taste regulates a wide range of behaviors, including caloric intake.
3) In humans, taste sensation is launched from taste buds in the mouth. These clusters contain 30 to 100 taste cells embedded in peg-like structures (papillae) on the tongue. At the tip of a taste bud is a pore formed by the bundling of taste cells, and extending through this pore into the oral cavity are finger-like protrusions (microvilli) from individual taste cells that bear the actual taste receptors. In general, humans perceive 5 basic taste qualities: salty (e.g., alkali metal ions), sour (e.g., hydrogen ions), sweet (e.g., carbohydrates), bitter (e.g., caffeine and quinine), and umami (the savory taste frequently associated with protein-rich foods.
Chem. & Eng. News http://www.cen-online.org
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THERMAL STIMULATION OF TASTE SENSATION
The term "chemoreceptors" refers to biological cells specialized to respond to chemical stimuli, and the function of such a cell is to signal to the nervous system a change in the chemical environment. In humans, for example, major use of chemoreceptors occurs in those parts of the body specialized for taste (gustatory sense) and smell (olfaction). Taste receptors are found in the epithelium of the tongue, and these receptors are responsible for sour, sweet, salty, and bitter sensations from food applied to the tongue. Taste receptors are also found in the pharynx and the upper part of the esophagus.
In contrast to olfactory receptors, taste receptors do not have their own output extensions (axons) to send signals to the central nervous system, but instead taste receptors stimulate the endings of nerve fibers that send input to the central nervous system ("afferent fibers"). Taste receptor cells are gathered into groups as "taste buds", and the sensing of taste stimuli occurs in finger-like projections (microvilli) at the surface of these taste buds, with various chemical mechanisms proposed to account for transduction of taste stimuli. In general, sourness depends primarily on the acidity of a chemical stimulus, and salty sensations are evoked by solutions with a high sodium concentration. Sweetness and bitterness, on the other hand, are apparently transduced by specific *receptor cell membrane receptors for sugars, amino acids, and other chemicals
Threshold concentrations for taste sensations produced by most ingested substances are relatively high. For example, the threshold concentration for sodium chloride is approximately 10 millimolar, for sucrose, 20 millimolar, for citric acid 2 millimolar. The threshold is much lower for certain bitter-tasting potentially dangerous plant compounds: the threshold concentration for quinine is 0.008 millimolar, and for strychnine 0.0001 millimolar.
In humans, approximately 4000 taste buds are distributed throughout the oral cavity and upper alimentary canal. Taste buds are approximately 50 microns wide at their base and approximately 80 microns long, each bud containing 30 to 100 taste receptor cells. Approximately 75 percent of all taste buds are found on the upper (dorsal) surface of the tongue.
The following points are made by A. Cruz and B.G. Green (Nature 2000 403:889):
1) The authors point out that the first electrophysiological recordings from animal and human taste nerves (in 1935 and 1985 respectively) provided clear evidence of thermal sensitivity, and studies have indicated that as many as half the neurons in the mammalian taste pathways respond to temperature. Since temperature has never been shown to induce sensations of taste, it has been assumed that thermal stimulation in the taste system is somehow nullified.
2) The authors report, however, that heating or cooling small areas of the tongue can in fact cause sensations of taste: warming the front (anterior) edge of the tongue (which is innervated by the chorda tympani nerve) from an initially cold temperature can evoke sweetness, whereas cooling can evoke sourness and/or saltiness. Thermal taste also occurs on the rear of the tongue (which is innervated by the glossopharyngeal nerve), but the relationship between temperature and taste is different in that location from that found in the front of the tongue.
3) The authors suggest these observations indicate the human taste system contains several different types of thermally sensitive neurons that normally contribute to the sensory code for taste, and that although there is evidence for neurons whose chemosensitive mechanisms are temperature sensitive, thermal sensitivity in some taste neurons may arise from cellular processes unrelated to chemosensory transduction.
Nature http://www.nature.com/nature
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Notes:
receptor cell membrane receptors: This phrase is a good illustration of the two uses of the term "receptor" in cell biology. Biological cells specialized to respond to specific physical or chemical stimuli are called "receptors cells", or merely "receptors". However, specific proteins or groups of proteins, embedded in the surface of a single cell, and which respond to interactions with specific ions, chemical groups, or molecules, and send molecular-level signals to the interior of the cell, are also called "receptors".
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