A proton current drives action potentials in genetically identified sour taste cells. Proc Natl Acad Sci USA

Department of Biological Sciences, Section of Neurobiology, University of Southern California, Los Angeles, CA 90089, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 12/2010; 107(51):22320-5. DOI: 10.1073/pnas.1013664107
Source: PubMed


Five tastes have been identified, each of which is transduced by a separate set of taste cells. Of these sour, which is associated with acid stimuli, is the least understood. Genetic ablation experiments have established that sour is detected by a subset of taste cells that express the TRP channel PKD2L1 and its partner PKD1L3, however the mechanisms by which this subset of cells detects acids remain unclear. Previous efforts to understand sour taste transduction have been hindered because sour responsive cells represent only a small fraction of cells in a taste bud, and numerous ion channels with no role in sour sensing are sensitive to acidic pH. To identify acid-sensitive conductances unique to sour cells, we created genetically modified mice in which sour cells were marked by expression of YFP under the control of the PKD2L1 promoter. To measure responses to sour stimuli we developed a method in which suction electrode recording is combined with UV photolysis of NPE-caged proton. Using these methods, we report that responses to sour stimuli are not mediated by Na(+) permeable channels as previously thought, but instead are mediated by a proton conductance specific to PKD2L1-expressing taste cells. This conductance is sufficient to drive action potential firing in response to acid stimuli, is enriched in the apical membrane of PKD2L1-expressing taste cells and is not affected by targeted deletion of the PKD1L3 gene. We conclude that, during sour transduction, protons enter through an apical proton conductance to directly depolarize the taste cell membrane.

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Available from: Emily R Liman, Jan 18, 2014
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    • "A recent study showed that acid response in mammalian sour taste cells is inhibited by zinc chloride but not by amiloride hydrochloride28. However, we found that pH-evoked response in Drosophila S-b sensilla was refractory to both zinc ion (P = 0.074 for 1 mM, P = 0.267 for 10 mM, Student’s t-test, Fig. 4b) and amiloride (P = 0.948, ANOVA, Fig. 4c). "
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    ABSTRACT: Drosophila melanogaster can taste various compounds and separate them into few basic categories such as sweet, bitter and salt taste. Here we investigate mechanisms underlying acid detection in Drosophila and report that the fly displays strong taste aversion to common carboxylic acids. We find that acid tastants act by the activation of a subset of bitter neurons and inhibition of sweet neurons. Bitter neurons begin to respond at pH 5 and show an increase in spike frequency as the extracellular pH drops, which does not rely on previously identified chemoreceptors. Notably, sweet neuron activity depends on the balance of sugar and acid tastant concentrations. This is independent of bitter neuron firing, and allows the fly to avoid acid-laced food sources even in the absence of functional bitter neurons. The two mechanisms may allow the fly to better evaluate the risk of ingesting acidic foods and modulate its feeding decisions accordingly.
    Preview · Article · Jun 2013 · Nature Communications
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    • "Sour transduction might also be mediated via channels sensitive to intracellular pH changes different from PKD2L1, e.g. proton inhibited K + channels, or via not yet identified proton channels (Chang et al. 2010). Surprisingly, the putative " sour " channel, PKD1L3/PKD2L1, seems to be inhibited by capsaicin pointing to a spicy-sour (chemesthetic) relation (Ishii et al. 2012). "
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    ABSTRACT: Spicy food does not only provide an important hedonic input in daily life, but has also been anedoctically associated to beneficial effects on our health. In this context, the discovery of chemesthetic trigeminal receptors and their spicy ligands has provided the mechanistic basis and the pharmacological means to investigate this enticing possibility. This review discusses in molecular terms the connection between the neurophysiology of pungent spices and the "systemic" effects associated to their trigeminality. It commences with a cultural and historical overview on the Western fascination for spices, and, after analysing in detail the mechanisms underlying the trigeminality of food, the main dietary players from the transient receptor potential (TRP) family of cation channels are introduced, also discussing the "alien" distribution of taste receptors outside the oro-pharingeal cavity. The modulation of TRPV1 and TRPA1 by spices is next described, discussing how spicy sensations can be turned into hedonic pungency, and analyzing the mechanistic bases for the health benefits that have been associated to the consumption of spices. These include, in addition to a beneficial modulation of gastro-intestinal and cardio-vascular function, slimming, the optimization of skeletal muscle performance, the reduction of chronic inflammation, and the prevention of metabolic syndrome and diabetes. We conclude by reviewing the role of electrophilic spice constituents on cancer prevention in the light of their action on pro-inflammatory and pro-cancerogenic nuclear factors like NFκB, and on their interaction with the electrophile sensor protein Keap1 and the ensuing Nrf2-mediated transcriptional activity. Spicy compounds have a complex polypharmacology, and just like any other bioactive agent, show a balance of beneficial and bad actions. However, at least for moderate consumption, the balance seems definitely in favour of the positive side, suggesting that a spicy diet, a caveman-era technology, could be seriously considered in addition to caloric control and exercise as a measurement to prevent and control many chronic diseases associate to malnutrition from a Western diet.
    Full-text · Article · Apr 2013 · Reviews of Physiology, Biochemistry and Pharmacology
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    • "The sense of taste guards the entrance to the alimentary canal and guides animals to reject foods that are perceived as too bitter or too sour. Detection of these taste qualities is usually attributed to taste buds which display specific receptor mechanisms for bitter, via the G protein-coupled receptor-coupled family of taste receptor type 2 (T2R) receptors, and for sour, probably involving an apical proton conductance (Chang et al. 2010). Despite the diversity of receptors and transduction cascades , transmission of taste information from the taste cells to the taste nerves requires functional P2X purinergic receptors (Finger et al. 2005). "
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    ABSTRACT: Mice lacking both the P2X2 and the P2X3 purinergic receptors (P2X-dblKO) exhibit loss of responses to all taste qualities in the taste nerves innervating the tongue. Similarly, these mice exhibit a near total loss of taste-related behaviors in brief access tests except for a near-normal avoidance of acidic stimuli. This persistent avoidance of acids despite the loss of gustatory neural responses to sour was postulated to be due to continued responsiveness of the superior laryngeal (SL) nerve. However, chemoresponses of the larynx are attributable both to taste buds and to free nerve endings. In order to test whether the SL nerve of P2X-dblKO mice remains responsive to acids but not to other tastants, we recorded responses from the SL nerve in wild-type (WT) and P2X-dblKO mice. WT mice showed substantial SL responses to monosodium glutamate, sucrose, urea, and denatonium-all of which were essentially absent in P2X-dblKO animals. In contrast, the SL nerve of P2X-dblKO mice exhibited near-normal responses to citric acid (50 mM) although responsiveness of both the chorda tympani and the glossopharyngeal nerves to this stimulus were absent or greatly reduced. These results are consistent with the hypothesis that the residual avoidance of acidic solutions by P2X-dblKO mice may be attributable to the direct chemosensitivity of nerve fibers innervating the laryngeal epithelium and not to taste.
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