Kengo Nomura: Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto, Kyoto 602-8566, Japan.
Miho Nakanishi: Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto, Kyoto 602-8566, Japan.
Fumiyoshi Ishidate: Center for Meso-Bio Single-Molecule Imaging, Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Kyoto 606-8501, Japan.
Kazumi Iwata: Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto, Kyoto 602-8566, Japan.
Akiyuki Taruno: Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto, Kyoto 602-8566, Japan; Japan Science and Technology Agency, PRESTO, Kawaguchi, Saitama 332-0012, Japan. Electronic address: taruno@koto.kpu-m.ac.jp.
Sodium taste regulates salt intake. The amiloride-sensitive epithelial sodium channel (ENaC) is the Na sensor in taste cells mediating attraction to sodium salts. However, cells and intracellular signaling underlying sodium taste in taste buds remain long-standing enigmas. Here, we show that a subset of taste cells with ENaC activity fire action potentials in response to ENaC-mediated Na influx without changing the intracellular Ca concentration and form a channel synapse with afferent neurons involving the voltage-gated neurotransmitter-release channel composed of calcium homeostasis modulator 1 (CALHM1) and CALHM3 (CALHM1/3). Genetic elimination of ENaC in CALHM1-expressing cells as well as global CALHM3 deletion abolished amiloride-sensitive neural responses and attenuated behavioral attraction to NaCl. Together, sodium taste is mediated by cells expressing ENaC and CALHM1/3, where oral Na entry elicits suprathreshold depolarization for action potentials driving voltage-dependent neurotransmission via the channel synapse. Thus, all steps in sodium taste signaling are voltage driven and independent of Ca signals. This work also reveals ENaC-independent salt attraction.
