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

Abstract Among the 5 taste qualities, salt is the least understood. The receptors, their expression pattern in taste cells, and the transduction mechanisms for salt taste are still unclear. Previous studies have suggested that low concentrations of NaCl are detected by the amiloride-sensitive epithelial Na+ channel (ENaC), which in other systems requires assembly of 3 homologous subunits (α, β, and γ) to form a functional channel. However, a new study from Lossow and colleagues, published in this issue of Chemical Senses, challenges that hypothesis by examining expression levels of the 3 ENaC subunits in individual taste cells using gene-targeted mice in combination with immunohistochemistry and in situ hybridization. Results show a lack of colocalization of ENaC subunits in taste cells as well as expression of subunits in taste cells that show no amiloride sensitivity. These new results question the molecular identity of the amiloride-sensitive Na+ conductance in taste cells.

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Self-Inhibition in Ca2+-Evoked Taste Responses: A Novel Tool for Functional Dissection of Salt Taste Transduction Mechanisms

Journal of Neurophysiology ◽

10.1152/jn.1998.79.2.911 ◽

1998 ◽

Vol 79 (2) ◽

pp. 911-921 ◽

Cited By ~ 7

Author(s):

Mamoun A. Kloub ◽

Gerard L. Heck ◽

John A. Desimone

Keyword(s):

Tight Junctions ◽

Ion Selectivity ◽

Critical Concentration ◽

Dependent Manner ◽

High Concentration ◽

Salt Taste ◽

Cation Conductance ◽

Taste Transduction ◽

Transduction Mechanisms ◽

Paracellular Pathways

Kloub, Mamoun A., Gerard L. Heck, and John A. DeSimone. Self-inhibition in Ca2+-evoked taste receptors: a novel tool for functional dissection of salt taste transduction mechanisms. J. Neurophysiol. 79: 911–921, 1998. Rat chorda tympani (CT) responses to CaCl2 were obtained during simultaneous current and voltage clamping of the lingual receptive field. Unlike most other salts, CaCl2 induced negatively directed transepithelial potentials and gave CT responses that were auto-inhibitory beyond a critical concentration. CT responses increased in a dose-dependent manner to ∼0.3 M, whereafter they decreased with increasing concentration. At concentrations where Ca2+ was self-inhibitory, it also inhibited responses to NaCl, KCl, and NH4Cl present in mixtures with CaCl2. Ca2+ completely blocked the amiloride-insensitive component of the NaCl CT response, the entire KCl-evoked CT response, and the high-concentration-domain CT responses of NH4Cl (≥0.3 M). The overlapping Ca2+-sensitivity between the responses of the three Cl− salts (Na+, K+, and NH+ 4) suggests a common, Ca2+-sensitive, transduction pathway. Extracellular Ca2+ has been shown to modulate the paracellular pathways in different epithelial cell lines by decreasing the water permeability and cation conductance of tight junctions. Ca2+-induced modulation of tight junctions is associated with Ca2+ binding to fixed negative sites. This results in a conversion of ion selectivity from cationic to anionic, which we also observed in our system through simultaneous monitoring of the transepithelial potential during CT recording. The data indicate the paracellular pathway as the stimulatory and modulatory site of CaCl2 taste responses. In addition, they indicate that important transduction sites for NaCl, KCl, and NH4Cl taste reception are accessible only through the paracellular pathways. More generally, they show that modulation of paracellular transport by Ca2+ in an intact epithelium has functional consequences at a systemic level.

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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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Taste reception

Physiological Reviews ◽

10.1152/physrev.1996.76.3.719 ◽

1996 ◽

Vol 76 (3) ◽

pp. 719-766 ◽

Cited By ~ 357

Author(s):

B. Lindemann

Keyword(s):

Cellular Response ◽

Second Messengers ◽

Membrane Receptors ◽

Major Advance ◽

Na Channels ◽

Cellular Mechanisms ◽

Salt Taste ◽

Taste Cells ◽

Taste Reception ◽

Salt Diffusion

Recent research on cellular mechanisms of peripheral taste has defined transduction pathways involving membrane receptors, G proteins, second messengers, and ion channels. Receptors for organic tastants received much attention, because they provide the specificity of a response. Their future cloning will constitute a major advance. Taste transduction typically utilizes two or more pathways in parallel. For instance, sweet-sensitive taste cells of the rat appear to respond to sucrose with activation of adenylyl cyclase, followed by adenosine 3',5'-cyclic monophosphate (cAMP)-dependent membrane events and Ca2+ uptake. The same cells respond differently to some artificial sweeteners, i.e., with activation of phospholipase C (PLC) followed by inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ release from intracellular stores. Some bitter tastants block K+ channels or initiate the cascade receptor G1 protein, PLC, IP3, and Ca2+ release or the cascade receptor alpha-gustducin, phosphodiesterase (PDE), cAMP decrease, and opening of cAMP-blocked channels. Membrane-permeant bitter tastants may elicit a cellular response by interacting with G protein, PLC, or PDE of the above cascades. Salt taste is initiated by current flowing into the taste cell through cation channels located in the apical membrane, even though basolateral channels may also contribute (following salt diffusion through paracellular pathways). In rodents, the Na+-specific component of salt taste is typically mediated by apical amiloride-sensitive Na+ channels, but less specific and not amiloride-sensitive taste components exist in addition. Sour taste may in part be mediated by amiloride-sensitive Na+ channels conducting protons, but other mechanisms certainly contribute. Thus the transduction of taste cells generally comprises parallel pathways. Furthermore, the transduction pathways vary with the location of taste buds on the tongue and, of course, across species of animals. To identify these pathways, to understand how they are controlled and why they evolved to this complexity are major goals of present research.

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Effects of voltage perturbation of the lingual receptive field on chorda tympani responses to Na+ and K+ salts in the rat: implications for gustatory transduction.

The Journal of General Physiology ◽

10.1085/jgp.104.5.885 ◽

1994 ◽

Vol 104 (5) ◽

pp. 885-907 ◽

Cited By ~ 58

Author(s):

Q Ye ◽

G L Heck ◽

J A DeSimone

Keyword(s):

Receptive Field ◽

Voltage Clamp ◽

Maximal Response ◽

Chorda Tympani ◽

Chorda Tympani Nerve ◽

Salt Taste ◽

Negative Voltage ◽

Voltage Clamp Condition ◽

Taste Cells ◽

Clamp Condition

Taste sensory responses from the chorda tympani nerve of the rat were recorded with the lingual receptive field under current or voltage clamp. Consistent with previous results (Ye, Q., G. L. Heck, and J. A. DeSimone. 1993. Journal of Neurophysiology. 70:167-178), responses to NaCl were highly sensitive to lingual voltage clamp condition. This can be attributed to changes in the electrochemical driving force for Na+ ions through apical membrane transducer channels in taste cells. In contrast, responses to KCl over the concentration range 50-500 mM were insensitive to the voltage clamp condition of the receptive field. These results indicate the absence of K+ conductances comparable to those for Na+ in the apical membranes of taste cells. This was supported by the strong anion dependence of K salt responses. At zero current clamp, the potassium gluconate (KGlu) threshold was > 250 mM, and onset kinetics were slow (12 s to reach half-maximal response). Faster onset kinetics and larger responses to KGlu occurred at negative voltage clamp (-50 mV). This indicates that when K+ ion is transported as a current, and thereby uncoupled from gluconate mobility, its rate of delivery to the K+ taste transducer increases. Analysis of conductances shows that the paracellular pathway in the lingual epithelium is 28 times more permeable to KCl than to KGlu. Responses to KGlu under negative voltage clamp were not affected by agents that are K+ channel blockers in other systems. The results indicate that K salt taste transduction is under paracellular diffusion control, which limits chemoreception efficiency. We conclude that rat K salt taste occurs by means of a subtight junctional transducer for K+ ions with access limited by anion mobility. The data suggest that this transducer is not cation selective which also accounts for the voltage and amiloride insensitive part of the response to NaCl.

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Signal transduction and TGF-β superfamily receptors

Biochemistry and Cell Biology ◽

10.1139/o96-033 ◽

1996 ◽

Vol 74 (3) ◽

pp. 299-314 ◽

Cited By ~ 22

Author(s):

Steven M. Kolodziejczyk ◽

Brian K. Hall

Keyword(s):

Signal Transduction ◽

G Protein ◽

Intracellular Signaling ◽

Specific Cell ◽

Type I ◽

Type Ii ◽

Type Iii ◽

Wide Range ◽

Transduction Mechanisms ◽

Kinase Cascade

The TGF-β superfamily includes a large number of related growth and differentiation factors expressed in virtually all phyla. Superfamily members bind to specific cell surface receptors that activate signal transduction mechanisms to elicit their effects. Candidate receptors fall into two primary groups, termed type I and type II receptors. Both types are serine/threonine kinases. Upon activation by the appropriate ligand, type I and type II receptors physically interact to form hetero-oligomers and subsequently activate intracellular signaling cascades, ultimately regulating gene transcription and expression. In addition, TGF-β binds to a third receptor class, type III, a membrane-anchored proteoglycan lacking the kinase activity typical of signal transducing molecules. Type III receptors appear to regulate ligand availability to type I and type II receptors. Although a number of transduction mechanisms may be available to TGF-β superfamily members, evidence gathered through the use of specific kinase and G-protein inhibitors and through assays measuring activation and levels of signaling intermediates suggests that at least one signaling pathway interacts with Ras and Raf proteins via a G-protein intermediate. Raf begins the cytoplasmic kinase cascade that leads to gene regulation. The myriad responses regulated by TGF-β superfamily members makes the understanding of signal transduction mechanisms utilized by these proteins of great interest to a wide range of biological disciplines.Key words: TGF-β superfamily, serine/threonine kinase receptors, G-proteins, Ras, cytoplasmic kinase cascade.

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A subset of broadly responsive Type III taste cells contribute to the detection of bitter, sweet and umami stimuli

10.1101/660589 ◽

2019 ◽

Cited By ~ 1

Author(s):

Debarghya Dutta Banik ◽

Eric D. Benfey ◽

Laura E. Martin ◽

Kristen E. Kay ◽

Gregory C. Loney ◽

...

Keyword(s):

Signaling Pathway ◽

Taste Receptor ◽

Live Cell ◽

Type I ◽

Type Ii Cells ◽

Type Ii ◽

Type Iii ◽

Umami Taste ◽

Taste Cells ◽

Multiple Signaling

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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Taste Transduction and Modulation

Physiology ◽

10.1152/physiologyonline.1988.3.3.109 ◽

1988 ◽

Vol 3 (3) ◽

pp. 109-112

Author(s):

SS Schiffman

Keyword(s):

Adenosine Receptor ◽

Potassium Salts ◽

Multiple Receptors ◽

Taste Transduction ◽

Taste Cells ◽

Transduction Mechanisms ◽

Sodium And Potassium

The application to the tongue of agents that interact with taste cells can tell us a great deal about transduction mechanisms that mediate taste. Separate pathways for Na+ and K+ appear to be part of the transduction mechanisms for the tastes of sodium and potassium salts. Caffeine and other methyl xanthines can potentiate certain tastes;this enhancement may involve the interaction of caffeine with an adenosine receptor. There is also evidence for glutamate and inosine receptors in addition to multiple receptors for sweet and bitter tastes.

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Transduction Mechanisms in Taste Cells

Transduction Channels in Sensory Cells ◽

10.1002/3527603913.ch7 ◽

2005 ◽

pp. 153-177 ◽

Cited By ~ 2

Author(s):

Kathryn Medler ◽

Sue C. Kinnamon

Keyword(s):

Taste Cells ◽

Transduction Mechanisms

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