Among the five basic taste modalities, sourness refers to our ability to detect acids within food. It not only helps us to maintain the acid-base balance and avoid the bad resources, but also provides us satisfying feelings during eating. Both human psychophysical and animal behavioral results demonstrated that sour sensation is elicited by protons dissociated from acids as well as by undissociated acid molecules. In peripheral taste organs, acids are detected by a population of taste receptor cells that express the trp channel PKD2L1; however, the cellular and molecular mechanisms of sour sensation are not clear yet. One problem in many previous studies is that sour-sensing cells were not distinguished from other populations of taste cells. Here by using BAC transgenic mice in which the sour-sensing taste cells were genetically labeled with YFP, we show that action potentials are evoked directly in PKD2L1-expressing sour-sensing taste cells by extracellular protons. This response to dissociated protons is driven by proton entry through a proton-selective conductance specifically expressed on the apical surface of these cells. Moreover, we show that undissociated weak acids evoke action potentials directly in PKD2L1-YFP taste cells as well. The response to weak acids is unlikely to be a consequence of inhibiting K⁺ channels by intracellular protons, as previously thought, but can be possibly attributed to the activation of voltage-gated Na⁺ channels. Together, we conclude that both protons and undissociated acid molecules elicit sour sensations by activating PKD2L1-expressing taste cells, but through different cellular mechanisms.
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