Sour Taste Sensation Research Articles

Sensing Sour: The OTOP1 Proton Channel from Function to Structure

The taste system evaluates chemicals to avoid toxins and identify nutrients. Among these is the ubiquitous hydrogen ion (H+), which when present at high concentrations elicits a sour taste sensation. In order to understand how taste receptor cells detect changes in H+ concentration (pH), we previously used patch clamp recording from sour-sensing taste receptor cells to identify a novel pH-sensitive proton-selective ionic current. To identify the gene that encodes this novel proton channel, we screened transcripts enriched in sour-sensing taste receptor cells for the ability to produce a proton current in a heterologous cell type. One gene, Otop1, encoding a protein (OTOP1) with twelve transmembrane domains, generated large inward currents in response to lowering extracellular pH. We showed that OTOP1 forms a proton channel, selective for H+ over other ions by a factor of a million-fold. To determine if Otop1 is required for sour taste, we generated and tested mice with an inactivating mutation of Otop1. In these mice, taste responses to acids were strongly attenuated, evidence that OTOP1 is a sour taste receptor. There are two murine homologs of Otop1, Otop2 and Otop3, which we find also encode proton channels. How OTOP channels are able to permeate H+ ions with such extraordinary selectivity is not known. The CryoEM structures of zebrafish OTOP1 and chicken OTOP3 show that the channel is a dimer, in which each subunit contains two domains (N and C) assembled so that the channel adopts a pseudotetrameric structure. However, unlike voltage-gated ion channels, the central cavity of OTOP channels is filled with cholesterol. OTOP channel isoforms are expressed in a diverse array of tissues, including in adipose tissue and the gastrointestinal tract, where they may be involved in pH regulation, ion transport or cellular signaling.

A biomimetic bioelectronic tongue: A switch for On- and Off- response of acid sensations

The perception of sour taste in mammals is important for its basic modality properties and avoiding toxic substances. We explore a biomimetic bioelectronic tongue, which integrate MEA (microelectrode array) and taste receptor cell for acid detection as a switch. However, the acid-sensing mechanism and coding of the taste receptor cells in the periphery is not well understood, with long-standing debate. Therefore, we firstly construct a Hodgkin-Huxley type mathematical model of whole-cell acid-sensing taste receptor cells based on the electrophysiologic patch clamp recordings with different acid sensitive receptor expressing and different acidic stimulations. ASICs and PKDL channels are two most promising candidates for acidic sensation. ASICs channels contribute to the On response, and PKDL channels coding the Offset stimulations respectively, which function as a pair for switch. Therefore, with the advantage of effective and noninvasive detection for MEA, a sour taste biosensor based on MEA and taste receptor cells was designed and established to detect sour response from the elementary acid sensitive taste receptor cells during and after stimulus. From simulation and extracelluar potential recordings, we found the biomimetic bioelectronic tongue was acid-sensitive, as acid stimulation pH decrease, the firing frequency significantly increase. Furthermore, this reliable and effective MEA based bioelectronic tongue functioned as a switch for stimulation On and Off. This study provided a powerful platform to recognize sour stimulation and help elucidate the sour taste sensation and coding mechanism.

Digital Lollipop

Among the five primary senses, the sense of taste is the least explored as a form of digital media applied in Human--Computer Interface. This article presents an experimental instrument, the Digital Lollipop, for digitally simulating the sensation of taste (gustation) by utilizing electrical stimulation on the human tongue. The system is capable of manipulating the properties of electric currents (magnitude, frequency, and polarity) to formulate different stimuli. To evaluate the effectiveness of this method, the system was experimentally tested in two studies. The first experiment was conducted using separate regions of the human tongue to record occurrences of basic taste sensations and their respective intensity levels. The results indicate occurrences of sour, salty, bitter, and sweet sensations from different regions of the tongue. One of the major discoveries of this experiment was that the sweet taste emerges via an inverse-current mechanism, which deserves further research in the future. The second study was conducted to compare natural and artificial (virtual) sour taste sensations and examine the possibility of effectively controlling the artificial sour taste at three intensity levels (mild, medium, and strong). The proposed method is attractive since it does not require any chemical solutions and facilitates further research opportunities in several directions including human--computer interaction, virtual reality, food and beverage, as well as medicine.

The clinical effects of Synsepalum dulcificum: a review.

Synsepalum dulcificum or the "miracle fruit" is well known for its taste-modifying ability. The aim of this review was to assess the published medically beneficial as well as potential characteristics of this fruit. A search in three databases, including PubMed, ScienceDirect, and Google Scholar, was made with appropriate keywords. The resulting articles were screened in different stages based on the title, abstract, and content. A total of nine articles were included in this review. This review summarized the findings of previously published studies on the effects of miracle fruit. The main studied characteristic of the fruit was its effect on the taste receptors, resulting in the sweet sensation when substances with acidic content were ingested. This effect was shown to be related to a glycoprotein called "miraculin." Other beneficial characteristics of this fruit were its antioxidant and anticancer abilities that are due to the various amides existing in the miracle fruit. Apart from the above, the other observed effect of this fruit was its antidiabetic effect that was tested in rats. Further studies should be conducted to establish the findings. The miracle fruit can be a healthy additive due to its unique characteristics, including sour taste sensation modification as well as its antioxidant and antidiabetic effects.

Might Helicobacter pylori infection be associated with distortion on taste perception?

Helicobacter pylori (H. pylori) has been found in dental plaque, saliva and lingual sites. To date, taste or olfaction disorders related to H. pylori infections have never been reported. In a review of the literature we found two papers just referring to a sour taste sensation during H. pylori infection. Studies in animal models suggest that changes in taste perception may relate to infections which damage taste buds. We observed an interesting clinical case of a 24-year-old Ghanaian woman with documented H. pylori gastric infection, complaining of cacosmia and cacogeusia. Taste evaluation indicated hypogeusia and highlighted a specific difficulty in discriminating between bitter and acid tastes. Saliva fluid was found positive for the ureA gene (H. pylori ureasi A).On the basis of this report, we hypothesize that taste perception might be correlated with a documented H. pylori infection. So, in a dyspeptic clinical picture in both pre and post diagnostic phase when H. pylori infection is suspected, taste evaluation might be important. Further studies are certainly needed in a large patient population to clarify the possible connection between H. pylori infection and smell–taste distortion.

Activation of Polycystic Kidney Disease-2-like 1 (PKD2L1)-PKD1L3 Complex by Acid in Mouse Taste Cells

Five basic tastes (bitter, sweet, umami, salty, and sour) are detected in the four taste areas where taste buds reside. Although molecular mechanisms for detecting bitter, sweet, and umami have been well clarified, those for sour and salty remain poorly understood. Several channels including acid-sensing ion channels have been proposed as candidate sour receptors, but they do not encompass all sour-sensing abilities in vivo. We recently reported a novel candidate for sour sensing, the polycystic kidney disease-2-like 1 (PKD2L1)-PKD1L3 channel complex. This channel is not a traditional ligand-gated channel and is gated open only after removal of an acid stimulus, called an off response. Here we show that off responses upon acid stimulus are clearly observed in native taste cells from circumvallate, but not fungiform papillae, of glutamate decarboxylase 67-green fluorescent protein (GAD67-GFP) knock-in mice, from which Type III taste cells can be visualized, using Ca(2+) imaging and patch clamp methods. Off responses were detected in most cells where PKD2L1 immunoreactivity was observed. Interestingly, the pH threshold for acid-evoked intracellular Ca(2+) increase was around 5.0, a value much higher than that observed in HEK293 cells expressing the PKD2L1-PKD1L3 complex. Thus, PKD2L1-PKD1L3-mediated acid-evoked off responses occurred both in HEK293 cells and in native taste cells, suggesting the involvement of the PKD2L1-PKD1L3 complex in acid sensing in vivo.

Off‐response property of an acid‐activated cation channel complex PKD1L3–PKD2L1

Ligand-gated ion channels are important in sensory and synaptic transduction. The PKD1L3-PKD2L1 channel complex is a sour taste receptor candidate that is activated by acids. Here, we report that the proton-activated PKD1L3-PKD2L1 ion channels have the unique ability to be activated after the removal of an acid stimulus. We refer to this property as the off-response (previously described as a delayed response). Electrophysiological analyses show that acid-induced responses are observed only after the removal of an acid solution at less than pH 3.0. A small increase in pH is sufficient for PKD1L3-PKD2L1 channel activation, after exposure to an acid at pH 2.5. These results indicate that this channel is a new type of ion channel-designated as an 'off-channel'-which is activated during stimulus application but not gated open until the removal of the stimulus. The off-response property of PKD1L3-PKD2L1 channels might explain the physiological phenomena occurring during sour taste sensation.

Peptides inhibitors of acid-sensing ion channels

Acid-sensing ion channels (ASICs) channels are proton-gated cationic channels mainly expressed in central and peripheric nervous system and related to the epithelial amiloride-sensitive Na + channels and to the degenerin family of ion channels. ASICs comprise four proteins forming functional channel subunits (ASIC1a, ASIC1b, ASIC2a, and ASIC3) and two proteins (ASIC2b and ASIC4) without yet known activators. Functional channels are activated by external pH variations ranging from pH 0.5 6.8 to 4.0 and currents are characterized by either rapid kinetics of inactivation (ASIC1a, ASIC1b, ASIC3) or slow kinetics of inactivation (ASIC2a) and sometimes the presence of a plateau phase (ASIC3). ASIC1a and ASIC3, which are expressed in nociceptive neurons, have been implicated in inflammation and knockout mice studies support the role of ASIC3 in various pain processes. ASIC1a seems more related to synaptic plasticity, memory, learning and fear conditioning in the CNS. ASIC2a contributes to hearing in the cochlea, sour taste sensation, and visual transduction in the retina. The pharmacology of ASICs is limited to rather nonselective drugs such as amiloride, nonsteroid anti-inflammatory drugs, and neuropeptides. Recently, two peptides, PcTx1 and APETx2, isolated from a spider and a sea anemone, have been characterized as selective and high-affinity inhibitors for ASIC1a and ASIC3 channels, respectively. PcTx1 inhibits ASIC1a homomers with an affinity of 0.7 nM (IC 50) without any effect on ASIC1a containing heteromers and thus helped to characterize ASIC1a homomeric channels in peripheric and central neurons. PcTx1 acts as a gating modifier since it shifts the channel from the resting to an inactivated state by increasing its affinity for H +. APETx2 is less selective since it inhibits several ASIC3-containing channels (IC 50 from 63 nM to 2 μM) and to date its mode of action is unknown. Nevertheless, APETx2 structure is related to other sea anemone peptides, which act as gating modifiers on Nav and Kv channels.

Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor

Animals use their gustatory systems to evaluate the nutritious value, toxicity, sodium content, and acidity of food. Although characterization of molecular identities that receive taste chemicals is essential, molecular receptors underlying sour taste sensation remain unclear. Here, we show that two transient receptor potential (TRP) channel members, PKD1L3 and PKD2L1, are coexpressed in a subset of taste receptor cells in specific taste areas. Cells expressing these molecules are distinct from taste cells having receptors for bitter, sweet, or umami tastants. The PKD2L1 proteins are accumulated at the taste pore region, where taste chemicals are detected. PKD1L3 and PKD2L1 proteins can interact with each other, and coexpression of the PKD1L3 and PKD2L1 is necessary for their functional cell surface expression. Finally, PKD1L3 and PKD2L1 are activated by various acids when coexpressed in heterologous cells but not by other classes of tastants. These results suggest that PKD1L3 and PKD2L1 heteromers may function as sour taste receptors.

A decade‐long sour‐taste sensation successfully treated with a proton‐pump inhibitor

We report a case study of a 54-year-old Japanese woman who persistently suffered from a sour-taste sensation in her mouth for 10 years, and was treated with a proton-pump inhibitor (PPI). She found sour-tasting meals irritable, and after eating such meals the sour-taste sensation worsened. She also complained of eructation and regurgitation. Upper gastrointestinal (GI) endoscopy showed duodenal erosion, superficial gastritis, and erosive oesophagitis. After 2 weeks of PPI therapy (lansoprazole, 30 mg day(-1)) the sour taste subjectively decreased to 70%, and after 6 weeks the symptoms disappeared. In addition to increased sensitivity of the mouth, gastro-oesophageal reflux might have created her obstinate sour-taste sensations. It is suggested that in such cases PPI therapy should be attempted.

Acidic stimuli activates two distinct pathways in taste receptor cells from rat fungiform papillae

A sour taste sensation may be produced when acidic stimuli interact with taste receptor cells (TRCs) on the dorsal surface of the tongue. We have searched for pathways in TRCs that may be activated by acidic stimuli using RT-PCR and changes in intracellular calcium (Ca 2+ I) induced by acidic stimuli in rat fungiform papillae. RT-PCR revealed the presence of proton-gated subunits ASIC-β and VR1. Ca 2+ imaging measurements of the TRCs revealed two distinct responses to acidic stimuli: Ca 2+ i was increased in 9% (28/308; Type I) and was decreased in 39% (121/308; Type II). Neither of these responses was affected by the removal of extracellular Ca 2+, indicating that the changes arise from the release and sequestration of Ca 2+ from intracellular stores. These responses were also not inhibited by the vanilloid receptor antagonist, capsazepine, suggesting they do not arise from the activation of vanilloid receptors. The Type I, but not the Type II response was inhibited by amiloride. Dose–response measurements for Types I and II responses yielded pH 50% of 4.8 and 4.9, respectively. Type II responses were inhibited by pertussis toxin, suggesting G-protein involvement. TRCs that exhibit Type II responses could also be activated by quinine (which increased Ca 2+ I) thus suggesting a mechanism by which the addition of acid may be suppressive to other chemical stimuli.

Chemosensory properties of sour tastants

In Experiment 1, a taste quality fractionation procedure was used to establish the degree to which sour and non-sour taste sensations are elicited by six concentrations of each of seven acids: citric, hydrochloric, sulfuric, lactic, malic, phosphoric and tartaric. In general, the acids differed significantly in their ability to elicit sour, salty and bitter sensations, with sulfuric and hydrochloric acids producing the smallest proportions of perceived sourness. Bitterness was found to be the largest non-sour sensation produced, followed by saltiness. The perceived taste qualities of the acids were stable across a wide range of concentrations. In Experiment 2 the extent to which the vapors of these test acids produce detectable intranasal non-gustatory sensations at concentration levels used in many human taste experiments was examined. All acids induced clear intranasal sensations at concentration levels used in some suprathreshold taste paradigms. The results suggest that a number of measures of sour taste sensation may be confounded by non-sour chemosensory factors, including intranasal stimulation.