The Candidate Sour Taste Receptor, PKD2L1, Is Expressed by Type III Taste Cells in the Mouse

ABSTRACTTaste receptor cells use multiple signaling pathways to detect chemicals in potential food items. These cells are functionally grouped into different types: Type I cells act as support cells and have glial-like properties; Type II cells detect bitter, sweet, and umami taste stimuli; and Type III cells detect sour and salty stimuli. We have identified a new population of taste cells that are broadly tuned to multiple taste stimuli including bitter, sweet, sour and umami. The goal of this study was to characterize these broadly responsive (BR) taste cells. We used an IP3R3-KO mouse (does not release calcium (Ca2+) from Type II cells when stimulated with bitter, sweet or umami stimuli) to characterize the BR cells without any potentially confounding input from Type II cells. Using live cell Ca2+ imaging in isolated taste cells from the IP3R3-KO mouse, we found that BR cells are a subset of Type III cells that respond to sour stimuli but also use a PLCβ3 signaling pathway to respond to bitter, sweet and umami stimuli. Unlike Type II cells, individual BR cells are broadly tuned and respond to multiple stimuli across different taste modalities. Live cell imaging in a PLCβ3-KO mouse confirmed that BR cells use a PLCβ3 signaling pathway to generate Ca2+ signals to bitter, sweet and umami stimuli. Analysis of c-Fos activity in the nucleus of the solitary tract (NTS) and short term behavioral assays revealed that BR cells make significant contributions to taste.

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The Cellular and Molecular Basis of Sour Taste

Annual Review of Physiology ◽

10.1146/annurev-physiol-060121-041637 ◽

2021 ◽

Vol 84 (1) ◽

Author(s):

Heather N. Turner ◽

Emily R. Liman

Keyword(s):

Taste Receptor ◽

Nerve Fibers ◽

Proton Channel ◽

Annual Review ◽

Publication Date ◽

Sour Taste ◽

Type Iii ◽

Afferent Nerve Fibers ◽

Classical Studies ◽

Unique Markers

Sour taste, the taste of acids, is one of the most enigmatic of the five basic taste qualities; its function is unclear and its receptor was until recently unknown. Sour tastes are transduced in taste buds on the tongue and palate epithelium by a subset of taste receptor cells, known as type III cells. Type III cells express a number of unique markers, including the PKD2L1 gene, which allow for their identification and manipulation. These cells respond to acid stimuli with action potentials and release neurotransmitters onto afferent nerve fibers, with cell bodies in geniculate and petrosal ganglia. Here, we review classical studies of sour taste leading up to the identification of the sour receptor as the proton channel, OTOP1. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Acid-Activated Cation Currents in Rat Vallate Taste Receptor Cells

Journal of Neurophysiology ◽

10.1152/jn.2002.88.1.133 ◽

2002 ◽

Vol 88 (1) ◽

pp. 133-141 ◽

Cited By ~ 68

Author(s):

Weihong Lin ◽

Tatsuya Ogura ◽

Sue C. Kinnamon

Keyword(s):

Taste Receptor ◽

Reversal Potential ◽

Equilibrium Potential ◽

Patch Clamp Technique ◽

Sour Taste ◽

Whole Cell Patch Clamp ◽

Current Voltage ◽

Taste Cells ◽

Stimulation Current ◽

Current Voltage Relationship

Sour taste is mediated by acids with the degree of sourness a function of proton concentration. Recently, several members of the acid-sensing ion channel subfamily (ASICs) were cloned from taste cells and proposed to mediate sour taste. However, it is not known whether sour responses in taste cells resemble the responses mediated by ASICs. Using the whole cell patch-clamp technique and Na+ imaging, we have characterized responses to acid stimuli in isolated rat vallate taste cells. Citric acid (pH 5) induced a large, rapidly activating inward current in most taste cells tested. The response showed various degrees of desensitization with prolonged stimulation. Current amplitudes were pH dependent, and adapting with acidic bath solutions reduced subsequent responses to acid stimulation. Amiloride (100–500 μM) partially and reversibly suppressed the acid-induced current. The current-voltage relationship showed reversal potential near the Na+equilibrium potential, suggesting that the current is carried predominantly by Na+. These data were consistent with Na+ imaging experiments showing that acid stimulation resulted in increases in intracellular Na+. Taken together, these data indicate that acid-induced currents in vallate taste cells share general properties with ASICs expressed in heterologous cells and sensory neurons that express ASIC subunits. The large amplitude of the current and its existence in a high percentage of taste cells imply that ASICs or ASIC-like channels may play a prominent role in sour-taste transduction.

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Faculty Opinions recommendation of Amiloride-Insensitive Salt Taste Is Mediated by Two Populations of Type III Taste Cells with Distinct Transduction Mechanisms.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726141438.793514748 ◽

2016 ◽

Author(s):

Sue Kinnamon

Keyword(s):

Salt Taste ◽

Type Iii ◽

Taste Cells ◽

Transduction Mechanisms ◽

Two Populations

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5-HT3A-driven green fluorescent protein delineates gustatory fibers innervating sour-responsive taste cells: A labeled line for sour taste?

The Journal of Comparative Neurology ◽

10.1002/cne.24209 ◽

2017 ◽

Vol 525 (10) ◽

pp. 2358-2375 ◽

Cited By ~ 6

Author(s):

J. M. Stratford ◽

E. D. Larson ◽

R. Yang ◽

E. Salcedo ◽

T. E. Finger

Keyword(s):

Green Fluorescent Protein ◽

Fluorescent Protein ◽

Sour Taste ◽

Taste Cells ◽

Green Fluorescent

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Taste Receptor Cell Responses to the Bitter Stimulus Denatonium Involve Ca2+ Influx Via Store-Operated Channels

Journal of Neurophysiology ◽

10.1152/jn.2002.87.6.3152 ◽

2002 ◽

Vol 87 (6) ◽

pp. 3152-3155 ◽

Cited By ~ 49

Author(s):

Tatsuya Ogura ◽

Robert F. Margolskee ◽

Sue C. Kinnamon

Keyword(s):

Prolonged Exposure ◽

Fluorescent Protein ◽

Bitter Taste ◽

Taste Receptor ◽

Taste Receptor Cell ◽

Cell Responses ◽

Necturus Maculosus ◽

Taste Cells ◽

Intracellular Ca ◽

Green Fluorescent

Previous studies in rat and mouse have shown that brief exposure to the bitter stimulus denatonium induces an increase in [Ca2+]i due to Ca2+ release from intracellular Ca2+ stores, rather than Ca2+influx. We report here that prolonged exposure to denatonium induces sustained increases in [Ca2+]i that are dependent on Ca2+ influx. Similar results were obtained from taste cells of the mudpuppy, Necturus maculosus, as well as green fluorescent protein (GFP) tagged gustducin-expressing taste cells of transgenic mice. In a subset of mudpuppy taste cells, prolonged exposure to denatonium induced oscillatory Ca2+responses. Depletion of Ca2+ stores by thapsigargin also induced Ca2+ influx, suggesting that Ca2+store-operated channels (SOCs) are present in both mudpuppy taste cells and gustducin-expressing taste cells of mouse. Further, treatment with thapsigargin prevented subsequent responses to denatonium, suggesting that the SOCs were the source of the Ca2+ influx. These data suggest that SOCs may contribute to bitter taste transduction and to regulation of Ca2+ homeostasis in taste cells.

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Mechanism of Sour Taste Transduction in Mudpuppy Taste Cells

Chemical Senses ◽

10.1201/9781003210146-13 ◽

2021 ◽

pp. 183-193

Author(s):

Sue C. Kinnamon

Keyword(s):

Sour Taste ◽

Taste Transduction ◽

Taste Cells

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Sodium/Calcium Exchangers Selectively Regulate Calcium Signaling in Mouse Taste Receptor Cells

Journal of Neurophysiology ◽

10.1152/jn.00118.2010 ◽

2010 ◽

Vol 104 (1) ◽

pp. 529-538 ◽

Cited By ~ 13

Author(s):

Steven A. Szebenyi ◽

Agnieszka I. Laskowski ◽

Kathryn F. Medler

Keyword(s):

Calcium Release ◽

Calcium Influx ◽

Taste Receptor ◽

Physiological Role ◽

Cytosolic Calcium ◽

Calcium Signals ◽

Sodium Calcium ◽

Signaling Mechanisms ◽

Taste Cells ◽

Mouse Taste

Taste cells use multiple signaling mechanisms to generate appropriate cellular responses to discrete taste stimuli. Some taste stimuli activate G protein coupled receptors (GPCRs) that cause calcium release from intracellular stores while other stimuli depolarize taste cells to cause calcium influx through voltage-gated calcium channels (VGCCs). While the signaling mechanisms that initiate calcium signals have been described in taste cells, the calcium clearance mechanisms (CCMs) that contribute to the termination of these signals have not been identified. In this study, we used calcium imaging to define the role of sodium-calcium exchangers (NCXs) in the termination of evoked calcium responses. We found that NCXs regulate the calcium signals that rely on calcium influx at the plasma membrane but do not significantly contribute to the calcium signals that depend on calcium release from internal stores. Our data indicate that this selective regulation of calcium signals by NCXs is due primarily to their location in the cell rather than to the differences in cytosolic calcium loads. This is the first report to define the physiological role for any of the CCMs utilized by taste cells to regulate their evoked calcium responses.

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Optogenetic Activation of Type III Taste Cells Modulates Taste Responses

Chemical Senses ◽

10.1093/chemse/bjaa044 ◽

2020 ◽

Vol 45 (7) ◽

pp. 533-539

Author(s):

Aurelie Vandenbeuch ◽

Courtney E Wilson ◽

Sue C Kinnamon

Keyword(s):

Light Response ◽

Sensory Nerves ◽

Taste Bud ◽

Chorda Tympani ◽

Chorda Tympani Nerve ◽

Type Iii ◽

Nonspecific Effects ◽

Taste Cells ◽

Specific Stimulation ◽

The Brain

Abstract Studies have suggested that communication between taste cells shapes the gustatory signal before transmission to the brain. To further explore the possibility of intragemmal signal modulation, we adopted an optogenetic approach to stimulate sour-sensitive (Type III) taste cells using mice expressing Cre recombinase under a specific Type III cell promoter, Pkd2l1 (polycystic kidney disease-2-like 1), crossed with mice expressing Cre-dependent channelrhodopsin (ChR2). The application of blue light onto the tongue allowed for the specific stimulation of Type III cells and circumvented the nonspecific effects of chemical stimulation. To understand whether taste modality information is preprocessed in the taste bud before transmission to the sensory nerves, we recorded chorda tympani nerve activity during light and/or chemical tastant application to the tongue. To assess intragemmal modulation, we compared nerve responses to various tastants with or without concurrent light-induced activation of the Type III cells. Our results show that light significantly decreased taste responses to sweet, bitter, salty, and acidic stimuli. On the contrary, the light response was not consistently affected by sweet or bitter stimuli, suggesting that activation of Type II cells does not affect nerve responses to stimuli that activate Type III cells.

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Physiological Evidence for Ionotropic and Metabotropic Glutamate Receptors in Rat Taste Cells

Journal of Neurophysiology ◽

10.1152/jn.1999.82.5.2061 ◽

1999 ◽

Vol 82 (5) ◽

pp. 2061-2069 ◽

Cited By ~ 51

Author(s):

Weihong Lin ◽

Sue C. Kinnamon

Keyword(s):

Glutamate Receptors ◽

Glutamate Receptor ◽

Metabotropic Glutamate Receptors ◽

Metabotropic Glutamate Receptor ◽

Monosodium Glutamate ◽

Taste Receptor ◽

Membrane Properties ◽

Group Iii ◽

Metabotropic Glutamate ◽

Taste Cells

Monosodium glutamate (MSG) elicits a unique taste in humans called umami. Recent molecular studies suggest that glutamate receptors similar to those in brain are present in taste cells, but their precise role in taste transduction remains to be elucidated. We used giga-seal whole cell recording to examine the effects of MSG and glutamate receptor agonists on membrane properties of taste cells from rat fungiform papillae. MSG (1 mM) induced three subsets of responses in cells voltage-clamped at −80 mV: a decrease in holding current (subset I), an increase in holding current (subset II), and a biphasic response consisting of an increase, followed by a decrease in holding current (subset III). Most subset II glutamate responses were mimicked by the ionotropic glutamate receptor (iGluR) agonist N-methyl-d-aspartate (NMDA). The current was potentiated by glycine and was suppressed by the NMDA receptor antagonist d(−)-2-amino-5-phosphonopentanoic acid (AP5). The group III metabotropic glutamate receptor (mGluR) agonistl-2-amino-4-phosphonobutyric acid (l-AP4) usually mimicked the subset I glutamate response. This hyperpolarizing response was suppressed by the mGluR antagonist (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG) and by 8-bromo-cAMP, suggesting a role for cAMP in the transduction pathway. In a small subset of taste cells, l-AP4 elicited an increase in holding current, resulting in taste cell depolarization under current clamp. Taken together, our results suggest that NMDA-like receptors and at least two types of group III mGluRs are present in taste receptor cells, and these may be coactivated by MSG. Further studies are required to determine which receptors are located on the apical membrane and how they contribute to the umami taste.

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