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Sour Ageusia in Two Individuals Implicates Ion Channels of the ASIC and PKD Families in Human Sour Taste Perception at the Anterior Tongue  [PDF]
Taufiqul Huque, Beverly J. Cowart, Luba Dankulich-Nagrudny, Edmund A. Pribitkin, Douglas L. Bayley, Andrew I. Spielman, Roy S. Feldman, Scott A. Mackler, Joseph G. Brand
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0007347
Abstract: Background The perception of sour taste in humans is incompletely understood at the receptor cell level. We report here on two patients with an acquired sour ageusia. Each patient was unresponsive to sour stimuli, but both showed normal responses to bitter, sweet, and salty stimuli. Methods and Findings Lingual fungiform papillae, containing taste cells, were obtained by biopsy from the two patients, and from three sour-normal individuals, and analyzed by RT-PCR. The following transcripts were undetectable in the patients, even after 50 cycles of amplification, but readily detectable in the sour-normal subjects: acid sensing ion channels (ASICs) 1a, 1β, 2a, 2b, and 3; and polycystic kidney disease (PKD) channels PKD1L3 and PKD2L1. Patients and sour-normals expressed the taste-related phospholipase C-β2, the δ-subunit of epithelial sodium channel (ENaC) and the bitter receptor T2R14, as well as β-actin. Genomic analysis of one patient, using buccal tissue, did not show absence of the genes for ASIC1a and PKD2L1. Immunohistochemistry of fungiform papillae from sour-normal subjects revealed labeling of taste bud cells by antibodies to ASICs 1a and 1β, PKD2L1, phospholipase C-β2, and δ-ENaC. An antibody to PKD1L3 labeled tissue outside taste bud cells. Conclusions These data suggest a role for ASICs and PKDs in human sour perception. This is the first report of sour ageusia in humans, and the very existence of such individuals (“natural knockouts”) suggests a cell lineage for sour that is independent of the other taste modalities.
Voltage-gated sodium channels in taste bud cells
Na Gao, Min Lu, Fernando Echeverri, Bianca Laita, Dalia Kalabat, Mark E Williams, Peter Hevezi, Albert Zlotnik, Bryan D Moyer
BMC Neuroscience , 2009, DOI: 10.1186/1471-2202-10-20
Abstract: We describe the molecular and histological expression profiles of cation channels involved in electrical signal transmission from apical to basolateral membrane domains. TRPM5 was positioned immediately beneath tight junctions to receive calcium signals originating from sweet, bitter, and umami receptor activation, while PKD2L1 was positioned at the taste pore. Using mouse taste bud and lingual epithelial cells collected by laser capture microdissection, SCN2A, SCN3A, and SCN9A voltage-gated sodium channel transcripts were expressed in taste tissue. SCN2A, SCN3A, and SCN9A were expressed beneath tight junctions in subsets of taste cells. SCN3A and SCN9A were expressed in TRPM5 cells, while SCN2A was expressed in TRPM5 and PKD2L1 cells. HCN4, a gene previously implicated in sour taste, was expressed in PKD2L1 cells and localized to cell processes beneath the taste pore.SCN2A, SCN3A and SCN9A voltage-gated sodium channels are positioned to sense initial depolarizing signals stemming from taste receptor activation and initiate taste cell action potentials. SCN2A, SCN3A and SCN9A gene products likely account for the tetrodotoxin-sensitive sodium currents in taste receptor cells.Taste buds house specialized neuroepithelial cells that sense and transmit information regarding the composition of food [1]. These taste cells express receptors for sweet, bitter, umami (the savory taste of glutamate), sour and salty tastants in apical microvilli facing the saliva [2,3]. Following taste receptor activation, taste cells depolarize and fire action potentials resulting in the release of neurotransmitters to nerve fibers innervating basolateral membranes [4,5]. Segregation of taste receptors at the taste pore from the machinery involved in transmitting signals to nerve fibers is mediated by tight junctions, specialized protein networks that separate apical and basolateral membrane domains [6].Information regarding the composition of food flows from the apical to the basolateral doma
Modeling and simulation of ion channels and action potentials in taste receptor cells
PeiHua Chen,Xiao-dong Liu,Wei Zhang,Jun Zhou,Ping Wang,Wei Yang,JianHong Luo
Science China Life Sciences , 2009, DOI: 10.1007/s11427-009-0138-9
Abstract: Based on patch clamp data on the ionic currents of rat taste receptor cells, a mathematical model of mammalian taste receptor cells was constructed to simulate the action potentials of taste receptor cells and their corresponding ionic components, including voltage-gated Na+ currents and outward delayed rectifier K+ currents. Our simulations reproduced the action potentials of taste receptor cells in response to electrical stimuli or sour tastants. The kinetics of ion channels and their roles in action potentials of taste receptor cells were also analyzed. Our prototype model of single taste receptor cell and simulation results presented in this paper provide the basis for the further study of taste information processing in the gustatory system.
Modeling and simulation of ion channels and action potentials in taste receptor cells

CHEN PeiHua,LIU Xiao-dong,ZHANG Wei,ZHOU Jun,WANG Ping,YANG Wei&,LUO JianHong,

中国科学C辑(英文版) , 2009,
Abstract: Based on patch clamp data on the ionic currents of rat taste receptor cells, a mathematical model of mammalian taste receptor cells was constructed to simulate the action potentials of taste receptor cells and their corresponding ionic components, including voltage-gated Na+ currents and outward delayed rectifier K+ currents. Our simulations reproduced the action potentials of taste receptor cells in response to electrical stimuli or sour tastants. The kinetics of ion channels and their roles in action potentials of taste receptor cells were also analyzed. Our prototype model of single taste receptor cell and simulation results presented in this paper provide the basis for the further study of taste information processing in the gustatory system.
The influence of sour taste and cold temperature in pharyngeal transit duration in patients with stroke
Cola, Paula Cristina;Gatto, Ana Rita;Silva, Roberta Gon?alves da;Spadotto, André Augusto;Schelp, Arthur Oscar;Henry, Maria Aparecida Coelho de Arruda;
Arquivos de Gastroenterologia , 2010, DOI: 10.1590/S0004-28032010000100004
Abstract: context: the effect of sour taste and food temperature variations in dysphagic patients has not been entirely clarified. objective: to determine the effect of sour and cold food in the pharyngeal transit times of patients with stroke. methods: patients participating in this study were 30 right-handed adults, 16 of which were male and 14 were female, aged 41 to 88 (average age 62.3 years) with ictus varying from 1 to 30 days (median of 6 days). to analyze the pharyngeal transit time a videofluoroscopy swallow test was performed. each patient was observed during swallow of a 5 ml paste bolus given by spoon, totaling four different stimuli (natural, cold, sour and cold sour), one at a time, room temperature (22oc) and cold (8oc) were used. later, the tests were analyzed using specific software to measure bolus transit time during the pharyngeal phase. results: the results showed that the pharyngeal transit time was significantly shorter during swallow of cold sour bolus when compared with other stimuli. conclusion - sour taste stimuli associated to cold temperature cause significant change in swallowing patterns, by shortening the pharyngeal transit time, which may lead to positive effects in patients with oropharyngeal dysphagia.
Acid Stimulation (Sour Taste) Elicits GABA and Serotonin Release from Mouse Taste Cells  [PDF]
Yijen A. Huang, Elizabeth Pereira, Stephen D. Roper
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025471
Abstract: Several transmitter candidates including serotonin (5-HT), ATP, and norepinephrine (NE) have been identified in taste buds. Recently, γ-aminobutyric acid (GABA) as well as the associated synthetic enzymes and receptors have also been identified in taste cells. GABA reduces taste-evoked ATP secretion from Receptor cells and is considered to be an inhibitory transmitter in taste buds. However, to date, the identity of GABAergic taste cells and the specific stimulus for GABA release are not well understood. In the present study, we used genetically-engineered Chinese hamster ovary (CHO) cells stably co-expressing GABAB receptors and Gαqo5 proteins to measure GABA release from isolated taste buds. We recorded robust responses from GABA biosensors when they were positioned against taste buds isolated from mouse circumvallate papillae and the buds were depolarized with KCl or a stimulated with an acid (sour) taste. In contrast, a mixture of sweet and bitter taste stimuli did not trigger GABA release. KCl- or acid-evoked GABA secretion from taste buds was Ca2+-dependent; removing Ca2+ from the bathing medium eliminated GABA secretion. Finally, we isolated individual taste cells to identify the origin of GABA secretion. GABA was released only from Presynaptic (Type III) cells and not from Receptor (Type II) cells. Previously, we reported that 5-HT released from Presynaptic cells inhibits taste-evoked ATP secretion. Combined with the recent findings that GABA depresses taste-evoked ATP secretion [1], the present results indicate that GABA and 5-HT are inhibitory transmitters in mouse taste buds and both likely play an important role in modulating taste responses.
Ghrelin Is Produced in Taste Cells and Ghrelin Receptor Null Mice Show Reduced Taste Responsivity to Salty (NaCl) and Sour (Citric Acid) Tastants  [PDF]
Yu-Kyong Shin,Bronwen Martin,Wook Kim,Caitlin M. White,Sunggoan Ji,Yuxiang Sun,Roy G. Smith,Jean Sévigny,Matthias H. Tsch?p,Stuart Maudsley,Josephine M. Egan
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012729
Abstract: The gustatory system plays a critical role in determining food preferences, food intake and energy balance. The exact mechanisms that fine tune taste sensitivity are currently poorly defined, but it is clear that numerous factors such as efferent input and specific signal transduction cascades are involved.
Amiloride-sensitive channels in type I fungiform taste cells in mouse
Aurelie Vandenbeuch, Tod R Clapp, Sue C Kinnamon
BMC Neuroscience , 2008, DOI: 10.1186/1471-2202-9-1
Abstract: Taste cell types were identified by their response to depolarizing voltage steps and their presence or absence of GFP fluorescence. TRPM5-GFP taste cells expressed large voltage-gated Na+ and K+ currents, but lacked voltage-gated Ca2+ currents, as expected from previous studies. Approximately half of the unlabeled cells had similar membrane properties, suggesting they comprise a separate population of Type II cells. The other half expressed voltage-gated outward currents only, typical of Type I cells. A single taste cell had voltage-gated Ca2+ current characteristic of Type III cells. Responses to amiloride occurred only in cells that lacked voltage-gated inward currents. Immunocytochemistry showed that fungiform taste buds have significantly fewer Type II cells expressing PLC signalling components, and significantly fewer Type III cells than circumvallate taste buds.The principal finding is that amiloride-sensitive Na+ channels appear to be expressed in cells that lack voltage-gated inward currents, likely the Type I taste cells. These cells were previously assumed to provide only a support function in the taste bud.At the peripheral taste system level, it is still unclear whether each taste quality is transduced by a separate population of taste cells, each connected to distinct nerve fibers (labelled-line model), or whether individual taste cells are sensitive to several taste modalities (across fiber pattern model). Currently, taste cells are categorized into three groups according to morphological, biochemical and physiological properties (for a review, see[1,2]). Type I cells make up about 50% of the total number of cells in a bud and are believed to have a support role, similar to glial cells in the nervous system. Type I cells wrap around other cells in the bud in a glial-like fashion [3]and express enzymes for inactivation and uptake of transmitters [4,5]. Notably, these cells have voltage-dependent outward currents, but they lack a voltage-gated inward cur
Behavioral characterization of mice lacking Trek channels  [PDF]
Kelsey Mirkovic,Florian Lesage,Kevin Wickman
Frontiers in Behavioral Neuroscience , 2012, DOI: 10.3389/fnbeh.2012.00060
Abstract: Two-pore domain K+ (K2P) channels are thought to underlie background K+ conductance in many cell types. The Trek subfamily of K2P channels consists of three members, Trek1/Kcnk2, Trek2/Kcnk10, and Traak/Kcnk4, all three of which are expressed in the rodent CNS. Constitutive ablation of the Trek1 gene in mice correlates with enhanced sensitivity to ischemia and epilepsy, decreased sensitivity to the effects of inhaled anesthetics, increased sensitivity to thermal and mechanical pain, and resistance to depression. While the distribution of Trek2 mRNA in the CNS is broad, little is known about the relevance of this Trek family member to neurobiology and behavior. Here, we probed the effect of constitutive Trek2 ablation, as well as the simultaneous constitutive ablation of all three Trek family genes, in paradigms that assess motor activity, coordination, anxiety-related behavior, learning and memory, and drug-induced reward-related behavior. No differences were observed between Trek2?/? and Trek1/2/Traak?/? mice in coordination or total distance traveled in an open-field. A gender-dependent impact of Trek ablation on open-field anxiety-related behavior was observed, as female but not male Trek2?/? and Trek1/2/Traak?/? mice spent more time in, and made a greater number of entries into, the center of the open-field than wild-type counterparts. Further evaluation of anxiety-related behavior in the elevated plus maze and light/dark box, however, did not reveal a significant influence of genotype on performance for either gender. Furthermore, Trek?/? mice behaved normally in tests of learning and memory, including contextual fear conditioning and novel object recognition, and with respect to opioid-induced motor stimulation and conditioned place preference (CPP). Collectively, these data argue that despite their broad distribution in the CNS, Trek channels exert a minimal influence on a wide-range of behaviors.
Ryanodine Receptors Selectively Interact with L Type Calcium Channels in Mouse Taste Cells  [PDF]
Michelle R. Rebello, Amanda B. Maliphol, Kathryn F. Medler
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0068174
Abstract: Introduction We reported that ryanodine receptors are expressed in two different types of mammalian peripheral taste receptor cells: Type II and Type III cells. Type II cells lack voltage-gated calcium channels (VGCCs) and chemical synapses. In these cells, ryanodine receptors contribute to the taste-evoked calcium signals that are initiated by opening inositol trisphosphate receptors located on internal calcium stores. In Type III cells that do have VGCCs and chemical synapses, ryanodine receptors contribute to the depolarization-dependent calcium influx. Methodology/Principal Findings The goal of this study was to establish if there was selectivity in the type of VGCC that is associated with the ryanodine receptor in the Type III taste cells or if the ryanodine receptor opens irrespective of the calcium channels involved. We also wished to determine if the ryanodine receptors and VGCCs require a physical linkage to interact or are simply functionally associated with each other. Using calcium imaging and pharmacological inhibitors, we found that ryanodine receptors are selectively associated with L type VGCCs but likely not through a physical linkage. Conclusions/Significance Taste cells are able to undergo calcium induced calcium release through ryanodine receptors to increase the initial calcium influx signal and provide a larger calcium response than would otherwise occur when L type channels are activated in Type III taste cells.
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