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Salt-Evoked Lingual Surface Potential in Humans

¹ Department of Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia, 23249; ² Department of Physiology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, 23249; ³ Medical Service, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia 23249

Submitted 20 February 2003; accepted in final form 7 May 2003

	ABSTRACT

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Salt sensing in animals involves the epithelial sodium channel (ENaC). If ENaC were involved in human salt sensing, then the lingual surface potential (LSP) would hyperpolarize when exposed to sodium. We developed a chamber to measure the LSP while different solutions superfused the surface of the tongue and a technique to adjust for the junction potentials induced by varying salt concentrations. Changing the superfusion solution from rinse solution (30 mM KCl) to 300 mM NaCl (+30 mM KCl) caused the LSP to hyperpolarize by 10.1 ± 0.7 mV (n = 13, P < 0.001). With repeated challenge the LSP response was reproducible. Increasing the Na concentration from 100 to 600 mM increased hyperpolarization by 35 ± 4.8% (n = 9, P < 0.001). To examine whether amiloride affects the LSP, 0.1 mM amiloride was added to 300 mM NaCl; it reduced the hyperpolarization by 18.5 ± 4.3% (P < 0.005, n = 11). However, the amiloride effect was not uniform: in six volunteers, amiloride inhibited the LSP by as much as 42%, while in five subjects, amiloride inhibited <5% of the LSP. In an amiloride sensitive volunteer, amiloride exerted 50% of its effect at 1 µM. In conclusion, we have demonstrated that the LSP can be measured in humans, that Na hyperpolarizes the LSP, that increasing the Na concentration increases LSP hyperpolarization, and that amiloride inhibits the Na evoked LSP in some humans. While ENaC is involved in sensing salt, its role appears to vary among individuals.

	INTRODUCTION

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Salt taste reception is mediated by taste receptor cells that form taste buds grouped in fungiform or foliate papillae on the anterolateral surface of the tongue. As suggested from psychophysical methods, human salt taste perception is determined by the chemical composition (NaCl being the saltiest) and the concentration of the salt, and it is decreased by amiloride, a specific inhibitor of the epithelial Na-channel (ENaC) (McCutcheon 1992; Schiffman et al. 1983; Tennissen 1992). So far, electrophysiological aspects of salt taste reception have been investigated only in animals. In these models, anterior lingual short circuit current and transepithelial potential or translingual potential (lingual surface potential) as well as the more proximal chorda tympani integrated response are attributed to the transepithelial movement of sodium (or other ions) through trans- and para-cellular pathways (Kloub et al. 1997, 1998; Ye et al. 1993, 1994). The electrophysiological responses evoked by Na-salts in animals are positively correlated to the concentration of the salt and are decreased by amiloride (Avenet and Lindemann 1988; DeSimone et al. 1981; Gilbertson et al. 1993; Simon and Garvin 1985; Ye et al. 1991). Importantly, in animal studies, the salt-evoked lingual surface potential correlates well with the chorda tympani response and taste sensory activation (DeSimone and Ferrell 1985). Here, for the first time, we show measurements of the human lingual surface potential and suggest it is feasible to analyze human taste perception using noninvasive electrophysiological methods.

	METHODS

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Subjects

Fourteen subjects (9 female, 5 male), aged 25–55 yr, participated in the protocols and abstained from ingesting food or liquid except water for 1 h prior to study. None of the subjects used medications known to affect taste. Subjects signed informed consent and were reimbursed for their time. The Institutional Review Board of McGuire VA Medical Center approved the protocols and the consent form.

Gustometer

When the concentration of NaCl superfusing the lingual surface is altered, the potential across the lingual epithelium will change if one of the ion pair, Na⁺ or Cl^–, transits the surface via a conductive pathway. The magnitude of the potential change should correlate with the magnitude of the conductive transport, and the sign of the evoked potential will differ if Na⁺ or Cl^– is the predominantly conducted ion. To detect evoked changes in the lingual surface potential, we constructed a molded resin gustometer with an embedded Ag/AgCl electrode, which adhered to the anterior lingual surface by vacuum (Fig. 1). Its design was adapted from one that has been successfully employed in animal studies (DeSimone et al. 2001; Heck et al. 1984; Kloub et al. 1998). The reference Ag/AgCl electrode was attached to the skin near the angle of the jaw. With this arrangement of electrodes, the lingual surface potential is negative-going if Na⁺ is the predominantly conducted ion. While this sign convention contrasts with reported measurements of lingual electrical events in animals, it is consistent with electrophysiological measurements in other Na⁺-transporting tissues and cells.

View larger version (27K): [in this window] [in a new window]   FIG. 1. Schematic. The gustometer with its embedded sensing Ag/AgCl electrode adhered to the anterior lingual surface by vacuum. The reference Ag/AgCl electrode was attached to the skin near the angle of the jaw. Test solutions flowed through the gustometer while a computer recorded the lingual surface potential. Details of the gustometer are illustrated in the inset.

The lingual surface potential detected by the electrodes was conditioned by an optically isolated and battery operated amplifier (DAM 50, World Precision Instruments, Sarasota, FL), digitized (Personal Daq 55, Iotech, Bedford Heights, OH), and recorded by computer at 1.3 Hz. Computer-controlled pumps (PHD 2000 Syringe Pump, Harvard Apparatus, Holliston, MA) propelled solutions at 333 µl/s through the 60-µl measuring chamber. The computer program recording the lingual surface potential and controlling the pumps was written in LabVIEW (version 5.1, National Instruments, Austin, TX).

Correction for junction potentials

A junction potential is generated whenever a solution contacts an electrode, and its magnitude is influenced by the ions in solution, their concentrations, and the type of electrode. In many electrophysiological experiments, the solution composition does not change significantly, and as a result, the junction potential is virtually constant throughout the experiment and is easily accounted for by "zeroing" the recording system at the beginning of the experiment. However, when studying the lingual surface potential, we planned to change the composition of the test solutions, and consequently we anticipated that the junction potential would change throughout the experiment. For example, the calibration traces, b and c, in Fig. 2 demonstrate that the junction potential varies widely as the solution contacting the gustometer electrode changes. To account for these varying nonbiologic junction potentials, gustometer calibration potentials were recorded before and after each experiment using the same protocol as the experiment. As illustrated in Fig. 2, the calibration signals were averaged and then subtracted from the experimental signal, yielding the lingual surface potential. During the calibration procedure a reference calomel electrode was located in the effluent fluid path.

View larger version (11K): [in this window] [in a new window]   FIG. 2. Example data and analysis. To detect the lingual surface potential (d) in the midst of the junction potentials induced by the different solutions, the calibration traces of the junction potentials were recorded before (b) and after (c) each experiment using the same protocol as the experiment (a). The calibration signals were averaged and then subtracted from the experimental signal, yielding the lingual surface potential: d = a – [(b + c)/2]. During the calibration procedures, the reference electrode was a calomel electrode located in the effluent tubing.

Preparative procedures and solutions

Prior to each use, the gustometer was disinfected with 3.4% gluteraldehyde (Cidex Plus, Advanced Sterilization Products, Irvine, CA), and its Ag/AgCl electrode was chloridized with 5.25% NaOCl (Clorox, Clorox Company, Oakland, CA). All solutions were prepared with distilled water and contained 30 mM KCl; the solutions were used at room temperature (20–22°C). NaCl and KCl were obtained from Fisher Scientific (Pittsburgh, PA), and amiloride was obtained from Sigma (St. Louis, MO).

Statistical methods

Data are presented as mean ± SE. Results were analyzed with paired and unpaired t-test, and significance was accepted if the two-tailed P value was <0.05.

	RESULTS

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First we demonstrated that, as in animals, salt evokes lingual surface potentials in humans. Figure 3A shows the effect of changing the rinse solution (30 mM KCl only) to 300 mM NaCl. Exposure to 300 mM NaCl for 30 s hyperpolarized the lingual surface potential by –10.1 ± 0.7 mV in 13 volunteers. The magnitude of the salt evoked potential ranged between –6.8 and –14.1 mV (Fig. 3A, period 1), indicating interindividual variability. To assess the reproducibility of the NaCl-evoked potential, the lingual surface was re-exposed to the NaCl solution after 4 min of exposure to rinse solution. The second exposure to NaCl evoked a potential that was 93 ± 2.6% (P < 0.05) of the initial value (Fig. 3A, period 2), indicating that the salt-evoked hyperpolarization of the lingual surface potential is reproducible. However, as shown in trace d in Fig. 2 after exposure to salt and then re-exposure to rinse solution, the lingual surface potential did not immediately or fully return to the baseline potential. Apparently the responsiveness of the lingual surface to salt is influenced by prior exposure to salt. This effect probably accounts for the slight reduction in evoked response to the second salt exposure (Fig. 3A).

View larger version (21K): [in this window] [in a new window]   FIG. 3. Effects of time, NaCl concentration, and amiloride on the lingual surface potential. A: exposure to 300 mM NaCl for 30 s hyperpolarized the lingual surface potential in periods 1 and 2. The periods were separated by 4 min of rinse. B: exposure to 600 mM NaCl evoked greater hyperpolarization of the LSP than did 100 mM NaCl. Two minutes of rinse separated the NaCl challenges. C: amiloride at a concentraion of 100 µM inhibited salt-evoked hyperpolarization. While 4 min of rinse separated the NaCl challenges, amiloride was added to the rinse 2 min before the NaCl/amiloride challenge.

To evaluate whether a relationship exists between the concentration of salt and the magnitude of the human lingual surface potential, solutions of 100 and 600 mM NaCl were applied separated by 2 min of rinse solution in nine subjects. As shown in Fig. 3B, 100 mM NaCl hyperpolarized the LSP by –7.5 ± 0.6 mV and 600 mM increased the hyperpolarization by an additional 35 ± 4.8% (P < 0.001), demonstrating a dose–response relationship between salt concentration and the lingual surface potential.

To assess whether the activity of the ENaC contributes to the human lingual surface potential evoked by salt, we used amiloride, an inhibitor of ENaC activity. First, amiloride-free solutions were applied to the lingual surface (in sequence, rinse for 2 min, 300 mM NaCl for 30 s, rinse for 2 min) and then similar solutions to which 100 µM amiloride had been added.¹ As shown in Fig. 3C, amiloride reduced the salt-evoked hyperpolarization by 18.5 ± 4.3% (P < 0.005, n = 11), indicating that ENaC has a role in the response to salt. To evaluate the interindividual sensitivity to amiloride, the data were adjusted for each subject's response to repeated exposure to salt as illustrated in Fig. 3A and noted above. The resulting normalized data shown in Fig. 4 demonstrate that the sensitivity to amiloride varied among subjects. Amiloride inhibited the salt evoked hyperpolarization in five subjects, had a modest effect in one subject, and had no effect in five subjects, whereas all subjects exhibited an amiloride-insensitive component of the salt evoked hyperpolarization.

View larger version (7K): [in this window] [in a new window]   FIG. 4. Inhibition of the lingual surface potential by amiloride. The effect of amiloride on the lingual surface potential was adjusted for the reproducibility of each individual's response to NaCl using the data in Fig. 3A: Percent Inhibition = (LSPamiloride/LSPpreamiloride)/(LSPperiod 2/LSPperiod 1) x 100.

To further characterize the relationship between the concentration of amiloride and the inhibition of the salt evoked hyperpolarization, we varied the amiloride concentration from 10^–8 to 10^–4 M while the salt concentration remained 150 mM in an individual who had exhibited amiloride sensitivity. As shown in Fig. 5, increasing the amiloride concentration progressively affected the lingual surface potential. Amiloride exerted 50% of its inhibitory effect at 1 µM in three repetitions.

View larger version (10K): [in this window] [in a new window]   FIG. 5. Dose response effect of amiloride. In an individual exhibiting amiloride sensitivity, the amiloride concentration was progressively increased from 10–8 to 10–4 M while the NaCl concentration remained 150 mM. In 3 repetitions of this protocol in the same individual, amiloride exerted 50% of its inhibitory effect at 1 µM.

	DISCUSSION

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Our data demonstrate that the lingual surface potential can be measured in humans noninvasively, that salt hyperpolarizes the surface potential in a dose dependent manner, and that amiloride reduces salt-evoked lingual hyperpolarization. Thus for the first time, we have provided direct evidence that the human tongue shares certain electrophysiological properties with animal models; specifically, sodium ions transit the human lingual surface via conductive pathways, including ENaC.

These observations are also consistent with results from psychophysical studies. For example, amiloride affects the lingual surface potential and influences salt perception in a subset of subjects (Anand and Zuniga 1997; McCutcheon 1992; Ossebaard and Smith 1995; Smith and Ossebaard 1995; Tennissen 1992; Tennissen and McCutcheon 1996). In sensitive subjects, amiloride reduces the ability of individuals to differentiate sodium concentrations (Anand and Zuniga 1997; McCutcheon 1992; Schiffman et al. 1983; Smith and Ossebaard 1995; Tennissen 1992; Tennissen and McCutcheon 1996) and alters the quality of salt taste, including the ability to distinguish sodium (and lithium) salts from potassium and ammonium salts (Ossebaard and Smith 1995, 1996; Ossebaard et al. 1997). At a concentration of 10 µM, amiloride exerts a near full effect on the amiloride sensitive component of the lingual surface potential (Fig. 4) and on the perception of salt (Smith and Ossebaard 1995). However, amiloride does not affect the larger portion of the salt-evoked lingual surface potential just as it fails to fully block salt perception (Anand and Zuniga 1997; McCutcheon 1992; Schiffman et al. 1983; Smith and Ossebaard 1995; Tennissen 1992; Tennissen and McCutcheon 1996). Thus in combination with the psychophysical data, our observations indicate that a significant portion of the sodium conductive pathways contributing to the lingual surface potential are present in taste receptor cells and play a role in the perception of saltiness.

While humans and animals respond to salt and amiloride, the responses differ in terms of amiloride's capacity to inhibit salt-induced electrical effects. In contrast to affecting the lingual potential in some humans only, amiloride affects electrical activity in almost all animals (Halpern 1998; Heck et al. 1984, 1989; Herness 1987; Ninomiya et al. 1989; Schiffman et al. 1990; Simon et al. 1993). In the individuals who exhibit amiloride sensitivity, the amiloride inhibitable portion of salt-evoked hyperpolarization appears to be smaller than that observed in animals (Avenet and Lindemann 1988; DeSimone et al. 1981, 2001; Gilbertson et al. 1993; Simon and Garvin 1985). However, when amiloride does block, the human IC₅₀ approximates the value observed in rodents, suggesting that there are quantitative, but not qualitative, differences between ENaC activity in humans and ENaC activity in animals (Avenet and Lindemann 1991; Doolin and Gilbertson 1996; Miyamoto et al. 2001). Our studies further indicate that humans fall into one of two taste categories: those that demonstrate both amiloride-sensitive and amiloride-insensitive salt taste, and those that show only amiloride-insensitive responses. A similar grouping has been observed among strains of mice (Ninomiya et al. 1989).

The heterogeneity of human sensitivity to amiloride may have a molecular basis as a preliminary report indicates that in fungiform papillae expression of ENaC subunits varies among individuals (Huque et al. 2002). When assessing mRNA for the subunit, a shortened version was identified in one of three volunteers and no subunit was detected in the other two volunteers. , , and subunits were discovered in all three volunteers, but an altered version of the subunit was noticed in one of the subjects. Interestingly, ENaC subunits are also not uniformly distributed in the rat tongue, as their expression varies from region to region and their cellular locations in taste receptor cells are influenced by mineralocorticoid stimulation (Kretz et al. 1999; Lin et al. 1999).

In summary, we have demonstrated that the human lingual surface potential can be measured and that these measurements are consistent with electrophysiological observations in animal models. Furthermore, these electrical measurements are consistent with human psychophysical observations. Since the lingual surface potential reflects taste receptor cell function and appears to reflect human perception, measuring the lingual surface potential is a novel technique for examining the taste sensory system in humans. As an objective measure, it should complement and extend the power of psychophysical approaches in the analysis of human taste perception.

	DISCLOSURES

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This work was supported by Merit Review grants from the Department of Veterans Affairs to G. M. Feldman and A. Mogyorósi.

	ACKNOWLEDGMENTS

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The authors thank V. A. Bickel for manufacturing the resin gustometers and N. L. Smith for technical assistance in conducting the studies.

	FOOTNOTES

 
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Amiloride had no independent effect on the lingual surface potential. In preliminary experiments when 100 µM amiloride was added to the rinse solution (30 mM KCl) superfusing the lingual surface the potential did not change. The lack of an independent amiloride effect was replicated in the protocol reported in the text and Figure 3c as the surface potential did not change when the solution superfusing the lingual surface was switched from the amiloride-free rinse solution to the rinse solution containing amiloride.

Address for reprint requests: G. M. Feldman, McGuire Veterans Affairs Medical Center, 1201 Broad Rock Blvd., Richmond, VA 23249 (E-mail: george.feldman{at}med.va.gov).

	REFERENCES

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION DISCLOSURES ACKNOWLEDGMENTS REFERENCES

 
Anand KK and Zuniga JR. Effect of amiloride on suprathreshold NaCl, LiCl, and KCl salt taste in humans. Physiol Behav 62: 925–929, 1997.[Medline]

Avenet P and Lindemann B. Amiloride-blockable sodium currents in isolated taste receptor cells. J Membr Biol 105: 245–255, 1988.[ISI][Medline]

Avenet P and Lindemann B. Noninvasive recording of receptor cell action potentials and sustained currents from single taste buds maintained in the tongue: the response to mucosal NaCl and amiloride. J Membr Biol 124: 33–41, 1991.[ISI][Medline]

DeSimone JA and Ferrell F. Analysis of amiloride inhibition of chorda tympani taste response of rat to NaCl. Am J Physiol 249: R52–R61, 1985.

DeSimone JA, Heck GL, and DeSimone SK. Active ion transport in dog tongue: a possible role in taste. Science 214: 1039–1041, 1981.[Abstract/Free Full Text]

DeSimone JA, Lyall V, Heck GL, Phan TH, Alam RI, Feldman GM, and Buch RM. A novel pharmacological probe links the amiloride-insensitive NaCl, KCl, and NH(4)Cl chorda tympani taste responses. J Neurophysiol 86: 2638–2641, 2001.[Abstract/Free Full Text]

Doolin RE and Gilbertson TA. Distribution and characterization of functional amiloride-sensitive sodium channels in rat tongue. J Gen Physiol 107: 545–554, 1996.[Abstract/Free Full Text]

Gilbertson TA, Roper SD, and Kinnamon SC. Proton currents through amiloride-sensitive Na⁺ channels in isolated hamster taste cells: enhancement by vasopressin and cAMP. Neuron 10: 931–942, 1993.[ISI][Medline]

Halpern BP. Amiloride and vertebrate gustatory responses to NaCl. Neurosci Biobehav Rev 23: 5–47, 1998.[ISI][Medline]

Heck GL, Mierson S, and DeSimone JA. Salt taste transduction occurs through an amiloride-sensitive sodium transport pathway. Science 223: 403–405, 1984.[Abstract/Free Full Text]

Heck GL, Persaud KC, and DeSimone JA. Direct measurement of translingual epithelial NaCl and KCl currents during the chorda tympani taste response. Biophys J 55: 843–857, 1989.[Abstract/Free Full Text]

Herness MS. Effect of amiloride on bulk flow and iontophoretic taste stimuli in the hamster. J Comp Physiol [A] 160: 281–288, 1987.[Medline]

Huque T, Wysocki L, Bayley D, Breslin PA, Spielman A, and Brand J. Expression of epithelial sodium channels in human fungiform papillae. Chem Senses 27: 669, 2002.

Kloub MA, Heck GL, and DeSimone JA. Chorda tympani responses under lingual voltage clamp: implications for NH4 salt taste transduction. J Neurophysiol 77: 1393–1406, 1997.[Abstract/Free Full Text]

Kloub MA, Heck GL, and DeSimone JA. Self-inhibition in Ca²⁺ -evoked taste responses: a novel tool for functional dissection of salt taste transduction mechanisms. J Neurophysiol 79: 911–921, 1998.[Abstract/Free Full Text]

Kretz O, Barbry P, Bock R, and Lindemann B. Differential expression of RNA and protein of the three pore-forming subunits of the amiloride-sensitive epithelial sodium channel in taste buds of the rat. J Histochem Cytochem 47: 51–64, 1999.[Abstract/Free Full Text]

Lin W, Finger TE, Rossier BC, and Kinnamon SC. Epithelial Na⁺ channel subunits in rat taste cells: localization and regulation by aldosterone. J Comp Neurol 405: 406–420, 1999.[ISI][Medline]

McCutcheon NB. Human psychophysical studies of saltiness suppression by amiloride. Physiol Behav 51: 1069–1074, 1992.[Medline]

Miyamoto T, Miyazaki T, Fujiyama R, Okada Y, and Sato T. Differential transduction mechanisms underlying NaCl- and KCl-induced responses in mouse taste cells. Chem Senses 26: 67–77, 2001.[Abstract/Free Full Text]

Ninomiya Y, Sako N, and Funakoshi M. Strain differences in amiloride inhibition of NaCl responses in mice, Mus musculus. J Comp Physiol [A] 166: 1–5, 1989.[Medline]

Ossebaard CA, Polet IA, and Smith DV. Amiloride effects on taste quality: comparison of single and multiple response category procedures. Chem Senses 22: 267–275, 1997.[Abstract/Free Full Text]

Ossebaard CA and Smith DV. Effect of amiloride on the taste of NaCl, Na-gluconate and KCl in humans: implications for Na⁺ receptor mechanisms. Chem Senses 20: 37–46, 1995.[Abstract/Free Full Text]

Ossebaard CA and Smith DV. Amiloride suppresses the sourness of NaCl and LiCl. Physiol Behav 60: 1317–1322, 1996.[Medline]

Schiffman SS, Lockhead E, and Maes FW. Amiloride reduces the taste intensity of Na⁺ and Li+ salts and sweeteners. Proc Natl Acad Sci USA 80: 6136–6140, 1983.[Abstract/Free Full Text]

Schiffman SS, Suggs MS, Cragoe EJ Jr., and Erickson RP. Inhibition of taste responses to Na⁺ salts by epithelial Na⁺ channel blockers in gerbil. Physiol Behav 47: 455–459, 1990.[Medline]

Simon SA, Elliott EJ, Erickson RP, and Holland VF. Ion transport across lingual epithelium is modulated by chorda tympani nerve fibers. Brain Res 615: 218–228, 1993.[ISI][Medline]

Simon SA and Garvin JL. Salt and acid studies on canine lingual epithelium. Am J Physiol 249: C398–C408, 1985.

Smith DV and Ossebaard CA. Amiloride suppression of the taste intensity of sodium chloride: evidence from direct magnitude scaling. Physiol Behav 57: 773–777, 1995.[Medline]

Tennissen AM. Amiloride reduces intensity responses of human fungiform papillae. Physiol Behav 51: 1061–1068, 1992.[Medline]

Tennissen AM and McCutcheon NB. Anterior tongue stimulation with amiloride suppresses NaCl saltiness, but not citric acid sourness in humans. Chem Senses 21: 113–120, 1996.[Abstract/Free Full Text]

Ye Q, Heck GL, and DeSimone JA. The anion paradox in sodium taste reception: resolution by voltage-clamp studies. Science 254: 724–726, 1991.[Abstract/Free Full Text]

Ye Q, Heck GL, and DeSimone JA. Voltage dependence of the rat chorda tympani response to Na⁺ salts: implications for the functional organization of taste receptor cells. J Neurophysiol 70: 167–178, 1993.[Abstract/Free Full Text]

Ye Q, Heck GL, and DeSimone JA. 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. J Gen Physiol 104: 885–907, 1994.[Abstract/Free Full Text]

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This Article Abstract Full Text (PDF) All Versions of this Article: 90/3/2060    most recent 00158.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Feldman, G. M. Articles by Lyall, V. Search for Related Content PubMed PubMed Citation Articles by Feldman, G. M. Articles by Lyall, V.