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      Molecular Basis of Infrared Detection by Snakes

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          Abstract

          Snakes possess a unique sensory system for detecting infrared radiation, enabling them to generate a ‘thermal image’ of predators or prey. Infrared signals are initially received by the pit organ, a highly specialized facial structure that is innervated by nerve fibers of the somatosensory system. How this organ detects and transduces infrared signals into nerve impulses is not known. Here we use an unbiased transcriptional profiling approach to identify TRPA1 channels as infrared receptors on sensory nerve fibers that innervate the pit organ. TRPA1 orthologues from pit bearing snakes (vipers, pythons, and boas) are the most heat sensitive vertebrate ion channels thus far identified, consistent with their role as primary transducers of infrared stimuli. Thus, snakes detect infrared signals through a mechanism involving radiant heating of the pit organ, rather than photochemical transduction. These findings illustrate the broad evolutionary tuning of TRP channels as thermosensors in the vertebrate nervous system.

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          Most cited references42

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          TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents.

          TRPA1 is an excitatory ion channel targeted by pungent irritants from mustard and garlic. TRPA1 has been proposed to function in diverse sensory processes, including thermal (cold) nociception, hearing, and inflammatory pain. Using TRPA1-deficient mice, we now show that this channel is the sole target through which mustard oil and garlic activate primary afferent nociceptors to produce inflammatory pain. TRPA1 is also targeted by environmental irritants, such as acrolein, that account for toxic and inflammatory actions of tear gas, vehicle exhaust, and metabolic byproducts of chemotherapeutic agents. TRPA1-deficient mice display normal cold sensitivity and unimpaired auditory function, suggesting that this channel is not required for the initial detection of noxious cold or sound. However, TRPA1-deficient mice exhibit pronounced deficits in bradykinin-evoked nociceptor excitation and pain hypersensitivity. Thus, TRPA1 is an important component of the transduction machinery through which environmental irritants and endogenous proalgesic agents depolarize nociceptors to elicit inflammatory pain.
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            Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin.

            Six members of the mammalian transient receptor potential (TRP) ion channels respond to varied temperature thresholds. The natural compounds capsaicin and menthol activate noxious heat-sensitive TRPV1 and cold-sensitive TRPM8, respectively. The burning and cooling perception of capsaicin and menthol demonstrate that these ion channels mediate thermosensation. We show that, in addition to noxious cold, pungent natural compounds present in cinnamon oil, wintergreen oil, clove oil, mustard oil, and ginger all activate TRPA1 (ANKTM1). Bradykinin, an inflammatory peptide acting through its G protein-coupled receptor, also activates TRPA1. We further show that phospholipase C is an important signaling component for TRPA1 activation. Cinnamaldehyde, the most specific TRPA1 activator, excites a subset of sensory neurons highly enriched in cold-sensitive neurons and elicits nociceptive behavior in mice. Collectively, these data demonstrate that TRPA1 activation elicits a painful sensation and provide a potential molecular model for why noxious cold can paradoxically be perceived as burning pain.
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              ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures.

              Mammals detect temperature with specialized neurons in the peripheral nervous system. Four TRPV-class channels have been implicated in sensing heat, and one TRPM-class channel in sensing cold. The combined range of temperatures that activate these channels covers a majority of the relevant physiological spectrum sensed by most mammals, with a significant gap in the noxious cold range. Here, we describe the characterization of ANKTM1, a cold-activated channel with a lower activation temperature compared to the cold and menthol receptor, TRPM8. ANKTM1 is a distant family member of TRP channels with very little amino acid similarity to TRPM8. It is found in a subset of nociceptive sensory neurons where it is coexpressed with TRPV1/VR1 (the capsaicin/heat receptor) but not TRPM8. Consistent with the expression of ANKTM1, we identify noxious cold-sensitive sensory neurons that also respond to capsaicin but not to menthol.
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                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                0028-0836
                1476-4687
                18 March 2010
                14 March 2010
                15 April 2010
                15 October 2010
                : 464
                : 7291
                : 1006-1011
                Affiliations
                [1 ]Department of Physiology, University of California, San Francisco, CA 94158-2517
                [2 ]Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158-2517
                [3 ]Howard Hughes Medical Institute, University of California, San Francisco, CA 94158-2517
                [4 ]California Institute for Quantitative Biosciences, University of California, San Francisco, CA 94158-2517
                [5 ]Natural Toxins Research Center, Texas A&M University-Kingsville, TX 78363
                Author notes
                Correspondence and requests for materials should be addressed to David Julius, Telephone: 415-476-0431, Telefax: 415-502-8644, julius@ 123456cmp.ucsf.edu , david.julius@ 123456ucsf.edu
                [*]

                denotes equal contribution

                [‡]

                Present address: Dept of Biology, University of Utah, 257 S 1400 E, Salt Lake City, UT 84112-0840

                Article
                nihpa182467
                10.1038/nature08943
                2855400
                20228791
                999de4e0-d12b-48d4-a42d-8524daae6dba

                Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Funding
                Funded by: National Institute of Neurological Disorders and Stroke : NINDS
                Award ID: R37 NS047723-19 ||NS
                Funded by: National Institute of Neurological Disorders and Stroke : NINDS
                Award ID: R37 NS047723-18 ||NS
                Funded by: National Institute of Neurological Disorders and Stroke : NINDS
                Award ID: R01 NS055299-04S1 ||NS
                Funded by: National Institute of Neurological Disorders and Stroke : NINDS
                Award ID: R01 NS055299-04 ||NS
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