Sour taste finds closure in a potassium channel.

Taste cells in taste buds of the mammalian tongue and oral cavity can detect five basic modalities: sweet, bitter, umami, salty, and sour. Each taste cell expresses distinct molecular sensors, such as G protein-coupled receptors or ion channels, which detect tastants (i.e., chemical stimuli that elicit taste sensation) and initiate an intracellular response that culminates in membrane depolarization and/or action potentials (APs) causing transmitter release. The race to solve themolecular identity of taste receptors more than 20 y ago sparked a revolution in gustatory physiology. The transduction components for sweet, bitter, umami, and salty taste have since been documented (1, 2), but sour taste remains poorly understood. The sour taste machinery has begun to emerge in recent years, but the intracellular response underlying sour taste detection is not known. In PNAS, Ye et al. (3) report a potassium (K) channel as a key component of sour taste transduction, which fills a significant gap in the field. Many ion channels have been proposed to mediate sour taste transduction, including a transient receptor potential (TRP) channel PKD2L1 and its partner PKD1L3 (4–11). Involvement of PKD family members in sour detection is supported by the fact that selective ablation of PKD2L1 cells nearly eliminates acidinduced responses in mouse gustatory nerve recordings (12). However, the functions of PKD2L1/PKD1L3 channels in sour taste remain enigmatic, given that genetic ablation of these channels has only a modest impact on acid-induced responses (13, 14). Nevertheless, PKD2L1 is a valuable molecular marker for sour cells (or type III taste cells), and its characterization has paved the way for the discovery of a Zn-sensitive proton conductance in PDK2L1 cells, which is believed to be the initial sour taste transduction event (15). The current consensus in the field is that upon acid stimulation (Fig. 1A), protons are shuttled into the cell via a proton channel, which ultimately leads to cell depolarization and the firing of APs. How the proton conductance mediates cell depolarization remains unknown, but previous studies have hinted at a potential role of cytosolic acidification in sour taste transduction. This hypothesis stems from the observation that weak acids, which can diffuse across the lipid bilayer, evoke stronger responses in the gustatory nerve compared with strong acids (at the same pH), which cannot diffuse across the cell membrane (16, 17) (Fig. 1A). Moreover, the proton conductance measured in sour taste cells in response to extracellular acid is likely insufficient to elicit APs on its own (18). Together, these data point to intracellular acidification as a second component of sour taste transduction. Until now, this hypothesis has not been directly tested. Here, Ye et al. (3) tested whether intracellular acidification mediates the sour taste response. To prevent contributions from endogenous proton conductance, Zn was used to block the proton channel in all experiments. By recording weak acid-induced responses from genetically labeled sour taste cells (PKD2L1-YFP) and nonsour taste cells (TRPM5 cells for sweet, umami, or bitter sensing), the authors found that APs are evoked in PKD2L1 cells but not in TRPM5 cells, supporting that Fig. 1. Potential contribution of the KIR2.1 channel in sour and nonsour taste cells. (A) In sour (PKD2L1) taste cells, weak acid causes stronger AP firing (Upper) than strong acid (Lower) at the same pH, presumably by intracellular acidification. (B, Upper) In nonsour (TRPM5) taste cells, weak acid stimulation does not cause AP firing, likely due to the large KIR2.1 current. (B, Lower) When the KIR2.1 current is mostly blocked, weak acid stimulation can cause AP firing.