Acid detection by taste receptor cells

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Abstract

Sourness is a primary taste quality that evokes an innate rejection response in humans and many other animals. Acidic stimuli are the unique sources of sour taste so a rejection response may serve to discourage ingestion of foods spoiled by acid producing microorganisms. The investigation of mechanisms by which acids excite taste receptor cells (TRCs) is complicated by wide species variability and within a species, apparently different mechanisms for strong and weak acids. The problem is further complicated by the fact that the receptor cells are polarized epithelial cells with different apical and basolateral membrane properties. The cellular mechanisms proposed for acid sensing in taste cells include, the direct blockage of apical K+ channels by protons, an H+-gated Ca2+ channel, proton conduction through apical amiloride-blockable Na+ channels, a Cl conductance blocked by NPPB, the activation of the proton-gated channel, BNC-1, a member of the Na+ channel/degenerin super family, and by stimulus-evoked changes in intracellular pH. Acid-induced intracellular pH changes appear to be similar to those reported in other mammalian acid-sensing cells, such as type-I cells of the carotid body, and neurons found in the ventrolateral medulla, nucleus of the solitary tract, the medullary raphe, and the locus coceuleus. Like type-I carotid body cells and brainstem neurons, isolated TRCs demonstrate a linear relationship between intracellular pH (pHi) and extracellular pH (pHo) with slope, ΔpHi/ΔpHo near unity. Acid-sensing cells also appear to regulate pHi when intracellular pH changes occur under iso-extracellular pH conditions, but fail to regulate their pH when pHi changes are induced by decreasing extracellular pH. We shall discuss the current status of proposed acid-sensing taste mechanisms, emphasizing pH-tracking in receptor cells.

Introduction

Among the chemoreceptors in the oral cavity is a subset that respond vigorously to acids. These are taste receptor cells (TRCs) that establish the response patterns in the peripheral gustatory system that ultimately produce the conscious perception of sourness. Sourness is one of the primary taste sensations (Scott and Plata-Salaman, 1991, Smith and Frank, 1993). It evokes an innate rejection response in infants (Beauchamp et al., 1991) and generally remains aversive to humans and most other animals throughout life. Aversive behavior toward sourness is easy to rationalize considering that acids uniquely comprise the class of sour stimuli, and acids are potentially harmful substances. Since each stimulus evoking sour sensations produces dissociable hydrogen ions, it would at first appear that TRCs are most likely extracellular pH detectors. On that basis the perception of sourness ought to be a graded function of stimulus pH. However, this proves not to be generally true. A poor correlation exists between the perception of sourness and stimulus pH, a finding that has been repeatedly confirmed in human psychophysical studies (Richards, 1898, Liljestrand, 1922, Beatty and Cragg, 1935, Ganzevles and Kroeze, 1987) and in human studies where the rate of acid-induced salivary secretion has been used as the index of sourness (Makhlouf and Blum, 1972). Recordings from gustatory afferents in rats have also been consistent in failing to show a strong correlation between stimulus pH and the neural response to particular acidic stimuli (Beidler, 1967, Beidler and Gross, 1971, Ogiso et al., 2000). These results beg the question: What specifically do TRCs sense when presented with acidic stimuli? In the following we will review a surprising diversity of transduction mechanisms that have been proposed for the sour taste modality and an equally surprising species variability. The reason for the plethora of proposed transduction mechanisms is, in part, the consequence of the high chemical reactivity of protons. At low concentration protons affect ion traffic across epithelia at the level of ion channels in the apical and basolateral cell membranes and in the paracellular shunt pathways connecting the cells. In addition they may affect these and other functional elements (e.g. neutral ion exchangers) from both outside and inside the cells (Lyall and Biber, 1994).

Section snippets

Sour perception in humans

One of the earliest observations in taste psychophysics is that acetic acid is perceived as more sour than HCl at the same pH, but that HCl is more sour than acetic acid at equimolar concentrations (Richards, 1898). It was soon recognized that at least part of this paradox derives from the fact that HCl is completely dissociated in solution while acetic acid is not. Beatty and Cragg (1935) used the perceived sourness of HCl to establish a scale against which other acids could be compared. On

Species differences in sour taste mechanisms

Insights into the cellular mechanisms of acid taste reception have been gleaned from a variety of animal models. Surprisingly many of the proposed mechanisms derived from studies on a given species fail to generalize fully to other species (Table 1). For that reason we will discuss these mechanisms according to species.

Evidence supporting a role for intracellular pH decrease in acid taste

Undissociated acid molecules as well as free protons interact directly with the apical membranes of TRCs. This interaction docs not seem to require specific H+ receptors on the apical membranes of TRCs. This conclusion is based on the observation that CT nerve responses to acids are not influenced by pretreatment of the tongue surface with protease (Ogiso et al., 2000) whereas that to sucrose are reduced effectively (Hiji, 1975). This implies that unlike sucrose sensing, membrane receptors or

Summary

In summary there is a remarkable diversity of mechanisms that appear to have a role in the transduction of the sour taste stimulus at the level of the TRCs. In some cases the mechanisms appear to be species specific. Most of these mechanisms involve putative cell membrane entry pathways for H+ ions or ion pathways modulated by H+ ions. However, weak organic acids can permeate cell membranes as undissociated molecules, suggesting that intracellular pH changes may also be important in acid taste

Acknowledgements

Supported by NIH grants DC-02422 and DC-00122 and the Department of Veterans Affairs.

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