Changes in taste receptor cell [Ca2+]i modulate chorda tympani responses to bitter, sweet, and umami taste stimuli

The relationship between taste receptor cell (TRC) intracellular Ca2+ ([Ca2+]i) and rat chorda tympani (CT) nerve responses to bitter (quinine and denatonium), sweet (sucrose, glycine, and erythritol), and umami [monosodium glutamate (MSG) and MSG + inosine 5′-monophosphate (IMP)] taste stimuli was investigated before and after lingual application of ionomycin (Ca2+ ionophore) + Ca2+, 1,2-bis(2-aminophenoxy)ethane- N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA-AM; Ca2+ chelator), U73122 (phospholipase C blocker), thapsigargin (Ca2+-ATPase blocker), and diC8-PIP2 (synthetic phosphatidylinositol 4,5-bisphosphate). The phasic CT response to quinine was indifferent to changes in [Ca2+]i. However, a decrease in [Ca2+]i inhibited the tonic part of the CT response to quinine. The CT responses to sweet and umami stimuli were indifferent to changes in TRC [Ca2+]i. However, a decrease in [Ca2+]i attenuated the synergistic effects of ethanol on the CT response to sweet stimuli and of IMP on the glutamate CT response. U73122 and thapsigargin inhibited the phasic and tonic CT responses to bitter, sweet, and umami stimuli. Although diC8-PIP2 increased the CT response to bitter and sweet stimuli, it did not alter the CT response to glutamate but did inhibit the synergistic effect of IMP on the glutamate response. The results suggest that bitter, sweet, and umami taste qualities are transduced by [Ca2+]i-dependent and [Ca2+]i-independent mechanisms. Changes in TRC [Ca2+]i in the BAPTA-sensitive cytosolic compartment regulate quality-specific taste receptors and ion channels that are involved in the neural adaptation and mixture interactions. Changes in TRC [Ca2+]i in a separate subcompartment, sensitive to inositol trisphosphate and thapsigargin but inaccessible to BAPTA and ionomycin + Ca2+, are associated with neurotransmitter release.

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Changes in taste receptor cell [Ca2+]i modulate chorda tympani responses to salty and sour taste stimuli

Journal of Neurophysiology ◽

10.1152/jn.00916.2011 ◽

2012 ◽

Vol 108 (12) ◽

pp. 3206-3220 ◽

Cited By ~ 10

Author(s):

John A. DeSimone ◽

ZuoJun Ren ◽

Tam-Hao T. Phan ◽

Gerard L. Heck ◽

Shobha Mummalaneni ◽

...

Keyword(s):

Apical Membrane ◽

Receptor Cell ◽

Imaging Techniques ◽

Taste Receptor ◽

Chorda Tympani ◽

Taste Receptor Cell ◽

Atpase Inhibitor ◽

Acetoxymethyl Ester ◽

Phasic Response ◽

Sour Taste

The relationship between taste receptor cell (TRC) Ca2+ concentration ([Ca2+]i) and rat chorda tympani (CT) nerve responses to salty [NaCl and NaCl+benzamil (Bz)] and sour (HCl, CO2, and acetic acid) taste stimuli was investigated before and after lingual application of ionomycin+Ca2+, 1,2-bis(2-aminophenoxy)ethane- N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA-AM), U73122 (phospholipase C blocker), and thapsigargin (Ca2+-ATPase inhibitor) under open-circuit or lingual voltage-clamp conditions. An increase in TRC [Ca2+]i attenuated the tonic Bz-sensitive NaCl CT response and the apical membrane Na+ conductance. A decrease in TRC [Ca2+]i enhanced the tonic Bz-sensitive and Bz-insensitive NaCl CT responses and apical membrane Na+ conductance but did not affect CT responses to KCl or NH4Cl. An increase in TRC [Ca2+]i did not alter the phasic response but attenuated the tonic CT response to acidic stimuli. A decrease in [Ca2+]i did not alter the phasic response but attenuated the tonic CT response to acidic stimuli. In a subset of TRCs, a positive relationship between [H+]i and [Ca2+]i was obtained using in vitro imaging techniques. U73122 inhibited the tonic CT responses to NaCl, and thapsigargin inhibited the tonic CT responses to salty and sour stimuli. The results suggest that salty and sour taste qualities are transduced by [Ca2+]i-dependent and [Ca2+]i-independent mechanisms. Changes in TRC [Ca2+]i in a BAPTA-sensitive cytosolic compartment regulate ion channels and cotransporters involved in the salty and sour taste transduction mechanisms and in neural adaptation. Changes in TRC [Ca2+]i in a separate subcompartment, sensitive to inositol trisphosphate and thapsigargin but inaccessible to BAPTA, are associated with neurotransmitter release.

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Effects of osmolarity on taste receptor cell size and function

AJP Cell Physiology ◽

10.1152/ajpcell.1999.277.4.c800 ◽

1999 ◽

Vol 277 (4) ◽

pp. C800-C813 ◽

Cited By ~ 33

Author(s):

Vijay Lyall ◽

Gerard L. Heck ◽

John A. DeSimone ◽

George M. Feldman

Keyword(s):

Cell Volume ◽

Receptor Cell ◽

Taste Receptor ◽

Chorda Tympani ◽

Taste Receptor Cell ◽

Salt Taste ◽

Receptor Cells ◽

Enhanced Ct ◽

And Function ◽

Osmotic Effects

Osmotic effects on salt taste were studied by recording from the rat chorda tympani (CT) nerve and by measuring changes in cell volume of isolated rat fungiform taste receptor cells (TRCs). Mannitol, cellobiose, urea, or DMSO did not induce CT responses. However, the steady-state CT responses to 150 mM NaCl were significantly increased when the stimulus solutions also contained 300 mM mannitol or cellobiose, but not 600 mM urea or DMSO. The enhanced CT responses to NaCl were reversed when the saccharides were removed and were completely blocked by addition of 100 μM amiloride to the stimulus solution. Exposure of TRCs to hyperosmotic solutions of mannitol or cellobiose induced a rapid and sustained decrease in cell volume that was completely reversible, whereas exposure to hypertonic urea or DMSO did not induce sustained reductions in cell volume. These data suggest that the osmolyte-induced increase in the CT response to NaCl involves a sustained decrease in TRC volume and the activation of amiloride-sensitive apical Na+ channels.

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Taste Receptor Cells in Mice Express Receptors for the Hormone Adiponectin

10.1101/335927 ◽

2018 ◽

Author(s):

Sean M. Crosson ◽

Andrew Marques ◽

Peter Dib ◽

Cedrick D. Dotson ◽

Steven D. Munger ◽

...

Keyword(s):

Cell Function ◽

Receptor Cell ◽

Taste Receptor ◽

Acid Oxidation ◽

Taste Receptor Cell ◽

Umami Taste ◽

Receptor Cells ◽

Taste Receptor Cells ◽

Immunohistochemical Studies ◽

Adipocyte Development

AbstractThe metabolic hormone adiponectin is secreted into the circulation by adipocytes, and mediates key biological functions including insulin sensitivity, adipocyte development, and fatty acid oxidation. Adiponectin is also abundant in saliva, where its functions are poorly understood. Here we report that murine taste receptor cells express adiponectin receptors, and may be a target for salivary adiponectin. Analysis of a transcriptome dataset obtained by RNA-seq analysis of purified circumvallate taste buds, revealed high expression levels for three adiponectin receptor types. Immunohistochemical studies showed that two of these receptors, AdipoR1 and T-cadherin, are localized to subsets of taste receptor cells. Immunofluorescence for T-cadherin was primarily co-localized with the Type 2 taste receptor cell marker phospholipase β2, suggesting that adiponectin signaling could impact sweet, bitter, or umami taste signaling. However, adiponectin null mice showed no differences in taste responsiveness compared to wildtype controls in brief-access taste testing. AAV-mediated overexpression of adiponectin in the salivary glands of adiponectin null mice did result in a small but significant increase in behavioral taste responsiveness to the fat emulsion Intralipid. Together, these results suggest that salivary adiponectin can effect taste receptor cell function, though its impact on taste responsiveness and peripheral taste coding remains unclear.

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Experimentally cross-wired lingual taste nerves can restore normal unconditioned gaping behavior in response to quinine stimulation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00668.2007 ◽

2008 ◽

Vol 294 (3) ◽

pp. R738-R747 ◽

Cited By ~ 14

Author(s):

Camille T. King ◽

Mircea Garcea ◽

Danielle S. Stolzenberg ◽

Alan C. Spector

Keyword(s):

Receptor Cell ◽

Recovery Of Function ◽

Taste Receptor ◽

Chorda Tympani ◽

Gustatory System ◽

Unresolved Issue ◽

Taste Receptor Cell ◽

Receptor Field ◽

Gustatory Nerve ◽

Posterior Tongue

Studies examining the effects of transection and regeneration of the glossopharyngeal (GL) and chorda tympani (CT) nerves on various taste-elicited behaviors in rats have demonstrated that the GL (but not the CT) nerve is essential for the maintenance of both an unconditioned protective reflex (gaping) and the neural activity observed in central gustatory structures in response to lingual application of a bitter substance. An unresolved issue, however, is whether recovery depends more on the taste nerve and the central circuits that it supplies and/or on the tongue receptor cell field being innervated. To address this question, we experimentally cross-wired these taste nerves, which, remarkably, can regenerate into parts of the tongue they normally do not innervate. We report that quinine-stimulated gaping behavior was fully restored, and neuronal activity, as assessed by Fos immunohistochemistry in the nucleus of the solitary tract and the parabrachial nucleus, was partially restored only if the posterior tongue (PT) taste receptor cell field was reinnervated; the particular taste nerve supplying the input was inconsequential to the recovery of function. Thus, PT taste receptor cells appear to play a privileged role in triggering unconditioned gaping to bitter tasting stimuli, regardless of which lingual gustatory nerve innervates them. Our findings demonstrate that even when a lingual gustatory nerve (the CT) forms connections with taste cells in a non-native receptor field (the PT), unconditioned taste rejection reflexes to quinine can be maintained. These findings underscore the extraordinary ability of the gustatory system to adapt to peripherally reorganized input for particular behaviors.

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N-geranyl cyclopropyl-carboximide modulates salty and umami taste in humans and animal models

Journal of Neurophysiology ◽

10.1152/jn.00124.2012 ◽

2013 ◽

Vol 109 (4) ◽

pp. 1078-1090 ◽

Cited By ~ 11

Author(s):

Mark L. Dewis ◽

Tam-Hao T. Phan ◽

ZuoJun Ren ◽

Xuanyu Meng ◽

Meng Cui ◽

...

Keyword(s):

Channel Blocker ◽

Monosodium Glutamate ◽

Taste Receptor ◽

Taste Intensity ◽

Chorda Tympani ◽

Wild Type ◽

Salt Taste ◽

Umami Taste ◽

Chicken Broth ◽

Related Compounds

Effects of N-geranyl cyclopropylcarboxamide (NGCC) and four structurally related compounds ( N-cyclopropyl E2,Z6-nonadienamide, N-geranyl isobutanamide, N-geranyl 2-methylbutanamide, and allyl N-geranyl carbamate) were evaluated on the chorda tympani (CT) nerve response to NaCl and monosodium glutamate (MSG) in rats and wild-type (WT) and TRPV1 knockout (KO) mice and on human salty and umami taste intensity. NGCC enhanced the rat CT response to 100 mM NaCl + 5 μM benzamil (Bz; an epithelial Na+ channel blocker) between 1 and 2.5 μM and inhibited it above 5 μM. N-(3-methoxyphenyl)-4-chlorocinnamid (SB-366791, a TRPV1t blocker) inhibited the NaCl+Bz CT response in the absence and presence of NGCC. Unlike the WT mice, no NaCl+Bz CT response was observed in TRPV1 KO mice in the absence or presence of NGCC. NGCC enhanced human salt taste intensity of fish soup stock containing 60 mM NaCl at 5 and 10 μM and decreased it at 25 μM. Rat CT responses to NaCl+Bz and human salt sensory perception were not affected by the above four structurally related compounds. Above 10 μM, NGCC increased the CT response to MSG+Bz+SB-366791 and maximally enhanced the response between 40 and 60 μM. Increasing taste cell Ca2+ inhibited the NGCC-induced increase but not the inosine monophosphate-induced increase in glutamate response. Addition of 45 μM NGCC to chicken broth containing 60 mM sodium enhanced the human umami taste intensity. Thus, depending upon its concentration, NGCC modulates salt taste by interacting with the putative TRPV1t-dependent salt taste receptor and umami taste by interacting with a Ca2+-dependent transduction pathway.

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Regulation of the Putative TRPV1t Salt Taste Receptor by Phosphatidylinositol 4, 5-Bisphosphate

Journal of Neurophysiology ◽

10.1152/jn.00883.2009 ◽

2010 ◽

Vol 103 (3) ◽

pp. 1337-1349 ◽

Cited By ~ 17

Author(s):

Vijay Lyall ◽

Tam-Hao T. Phan ◽

ZuoJun Ren ◽

Shobha Mummalaneni ◽

Pamela Melone ◽

...

Keyword(s):

Monosodium Glutamate ◽

Taste Receptor ◽

Receptor Protein ◽

Chorda Tympani ◽

Sprague Dawley ◽

Salt Taste ◽

Sprague Dawley Rats ◽

Enhanced Ct ◽

Biphasic Effect ◽

Phosphatidylinositol 4

Regulation of the putative amiloride and benzamil (Bz)-insensitive TRPV1t salt taste receptor by phosphatidylinositol 4,5-bisphosphate (PIP2) was studied by monitoring chorda tympani (CT) taste nerve responses to 0.1 M NaCl solutions containing Bz (5 × 10−6 M; a specific ENaC blocker) and resiniferatoxin (RTX; 0–10 × 10−6 M; a specific TRPV1 agonist) in Sprague-Dawley rats and in wildtype (WT) and TRPV1 knockout (KO) mice. In rats and WT mice, RTX elicited a biphasic effect on the NaCl + Bz CT response, increasing the CT response between 0.25 × 10−6 and 1 × 10−6 M. At concentrations >1 × 10−6 M, RTX inhibited the CT response. An increase in PIP2 by topical lingual application of U73122 (a phospholipase C blocker) or diC8-PIP2 (a short chain synthetic PIP2) inhibited the control NaCl + Bz CT response and decreased its sensitivity to RTX. A decrease in PIP2 by topical lingual application of phenylarsine oxide (a phosphoinositide 4 kinase blocker) enhanced the control NaCl + Bz CT response, increased its sensitivity to RTX stimulation, and inhibited the desensitization of the CT response at RTX concentrations >1 × 10−6 M. The ENaC-dependent NaCl CT responses were not altered by changes in PIP2. An increase in PIP2 enhanced CT responses to sweet (0.3 M sucrose) and bitter (0.01 M quinine) stimuli. RTX produced the same increase in the Bz-insensitive Na+response when present in salt solutions containing 0.1 M NaCl + Bz, 0.1 M monosodium glutamate + Bz, 0.1 M NaCl + Bz + 0.005 M SC45647, or 0.1 M NaCl + Bz + 0.01 M quinine. No effect of RTX was observed on CT responses in WT mice and rats in the presence of the TRPV1 blocker N-(3-methoxyphenyl)-4-chlorocinnamide (1 × 10−6 M) or in TRPV1 KO mice. We conclude that PIP2 is a common intracellular effector for sweet, bitter, umami, and TRPV1t-dependent salt taste, although in the last case, PIP2 seems to directly regulate the taste receptor protein itself, i.e., the TRPV1 ion channel or its taste receptor variant, TRPV1t.

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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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Differential temperature dependence of taste nerve responses to various taste stimuli in dogs and rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1991.261.6.r1402 ◽

1991 ◽

Vol 261 (6) ◽

pp. R1402-R1408 ◽

Cited By ~ 6

Author(s):

M. Nakamura ◽

K. Kurihara

Keyword(s):

Acetic Acid ◽

Temperature Dependence ◽

Temperature Change ◽

Dose Response ◽

Monosodium Glutamate ◽

Taste Receptor ◽

Chorda Tympani ◽

Chorda Tympani Nerve ◽

Response Curves ◽

Tonic Response

The temperature dependence of the canine and rat chorda tympani nerve responses to various taste stimuli was examined. The temperature dependence greatly varied with species of stimuli. In the dog, the tonic responses to fructose, sucrose, acetic acid, and guanosine 5'-monophosphate (GMP) and the response induced by the synergism between monosodium glutamate (MSG) and GMP showed peaks at approximately 30 degrees C, whereas those to NaCl, NH4Cl, and MSG showed peaks between 10 and 20 degrees C. In the rat, the tonic response to NH4Cl increased with an increase in temperature up to 45 degrees C, whereas the responses to other stimuli examined showed peaks at approximately 30 degrees C. The responses to glycine, sucrose, and quinine showed sharp temperature dependence, and the responses to acids (HCl and acetic acid) and salts (NaCl and KCl) showed relatively flat dependence. The effects of the temperature change on dose-response curves for fructose, NH4Cl, and GMP were examined using dogs. The temperature change did not practically affect the thresholds for these stimuli and affected the magnitude of the responses to higher concentrations of stimuli. The origins of the temperature dependence were discussed in terms of taste receptor mechanisms.

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