TRPs in taste and chemesthesis

Abstract

TRP channels are expressed in taste buds, nerve fibers, and keratinocytes in the oronasal cavity. These channels play integral roles in transducing chemical stimuli, giving rise to sensations of taste, irritation, warmth, coolness, and pungency. Specifically, TRPM5 acts downstream of taste receptors in the taste transduction pathway. TRPM5 channels convert taste-evoked intracellular Ca(2+) release into membrane depolarization to trigger taste transmitter secretion. PKD2L1 is expressed in acid-sensitive (sour) taste bud cells but is unlikely to be the transducer for sour taste. TRPV1 is a receptor for pungent chemical stimuli such as capsaicin and for several irritants (chemesthesis). It is controversial whether TRPV1 is present in the taste buds and plays a direct role in taste. Instead, TRPV1 is expressed in non-gustatory sensory afferent fibers and in keratinocytes of the oronasal cavity. In many sensory fibers and epithelial cells lining the oronasal cavity, TRPA1 is also co-expressed with TRPV1. As with TRPV1, TRPA1 transduces a wide variety of irritants and, in combination with TRPV1, assures that there is a broad response to noxious chemical stimuli. Other TRP channels, including TRPM8, TRPV3, and TRPV4, play less prominent roles in chemesthesis and no known role in taste, per se. The pungency of foods and beverages is likely highly influenced by the temperature at which they are consumed, their acidity, and, for beverages, their carbonation. All these factors modulate the activity of TRP channels in taste buds and in the oronasal mucosa.

Fig. 1. “Word clouds” showing the prominence of literature references to TRP channels in taste (top) and chemesthesis (bottom)

Abstracts of publications describing TRP channels in studies on taste and chemesthesis were searched. The size of the font is proportional to the number of times a given TRP channel is mentioned in these abstracts (see http://www.wordle.net/). This representation gives an approximation of how well-studied are these TRP channels in taste and chemesthesis. For taste, TRPM5 > TRPV1 ≫ PKD2L1 ~ TRPA1 >PKD1L3 >TRPMb >TRPV4 ≫ TRPV3. For chemesthesis, TRPV1 ≫ TRPA1 >TRPM8 ≫ TRPM5 >TRPV4 >TRPV2 >TRPV3

Fig. 2. The three major classes of taste cells

This classification incorporates ultrastructural features, patterns of gene expression, and the functions of each of types I, II (Receptor), and III (Presynaptic) taste cells. Type I cells (grey) degrade or absorb neurotransmitters. They also may clear extracellular K⁺ that accumulates after action potentials (shown as starburst symbols) in Receptor (yellow) and Presynaptic (green) cells. K⁺ may be extruded through an apical K channel such as ROMK. Salty taste may be transduced by some type I cells, but this remains uncertain. Sweet, bitter, and umami taste compounds activate Receptor cells, inducing them to release ATP through pannexin1 (Panx1) (Huang et al. 2007; Romanov et al. 2007) or CALHM1 (Taruno et al. 2013) channels. The extracellular ATP excites ATP receptors (P2X, P2Y) on sensory nerve fibers and on taste cells. Presynaptic cells, in turn, release serotonin (5-HT) and GABA, which inhibit Receptor cells. Sour stimuli (and carbonation, not depicted) directly activate presynaptic cells. Only presynaptic cells form ultrastructurally identifiable synapses with nerves. Starburst symbols denote action potentials. Tables below the cells list some of the proteins that are expressed in a cell type—selective manner. Modified from Chaudhari and Roper (2010)

Fig. 3. The oronasal cavity and its innervation, showing TRP channels involved in taste and chemesthesis

TRP channels are expressed in sensory ganglion neurons, their axon terminals, and in epithelial keratinocytes throughout the oronasal cavity. The TRP channels illustrated here have known or implied functions in gustation and chemesthesis. Other TRP channels are expressed in these sites, but their functions in taste and chemesthesis are not well understood. Drawing courtesy of Patrick Lynch, Yale University

Fig. 4. Canonical transduction pathway for sweet, bitter, and umami taste stimuli

These taste compounds activate G protein-coupled taste receptors that are expressed in taste Receptor (type II) cells. Taste receptor activation leads to IP3-mediated intracellular Ca²⁺ release, TRPM5 opening, and ultimately, transmitter secretion from Receptor cells. Reviewed in Chaudhari and Roper (2010)

Fig. 5. Certain TRP channels involved in chemesthesis are also thermoreceptors

Mammalian TRP ion channels detect a broad range of temperatures. Their in vitro properties predict the thermal zones each channel potentially mediates. A role for TRPV3 and TRPV4 in thermal detection, however, is debatable (Huang et al. 2011). Many of these channels are also activated by plant derivatives, some of which provide distinct sensations of temperature. Examples of these plants are shown at top of figure. Modified from McKemy (2007)

Fig. 6. Distribution of rat trigeminal ganglion neurons that express TRPM8, TRPA1, and TRPV1

There is extensive co-expression of TRPA1 and TRPV1 in many of these sensory ganglion cells. A separate population of neurons expresses TRPM8. This Venn diagram was created from data published in Kobayashi et al. (2005)

Fig. 7. Acidic food and drink are likely to influence TRP channel activity in the oronasal epithelium

Mineral (strong) acids, for example, phosphoric acid in cola drinks, might be expected to penetrate into and acidify the interstitial fluid spaces in the mucosal epithelium (increase [H⁺]_o). This would enhance TRPV1 channel activity in cells and nerve fibers there. Alternatively, weak acids such as acetic acid or CO₂ from carbonated drinks will diffuse across cell membranes, dissociate inside the cells, and acidify the cytosol (increase [H⁺]_i). This would be expected to occur inside nerve terminals, keratinocytes, and taste bud cells, as shown here. Intracellular acidification enhances TRPA1 channel activity and suppresses TRPV1 channels. Drawing of taste bud from Parker (1912)