Science Topics – 140

As dietary sodium is a risk factor for cardiovascular diseases, a reduction in salt intake is recommended worldwide. Sodium ion (Na⁺) in table salt (NaCl) evokes the attractive component of salty taste (sodium taste), and the Na⁺ sensor in taste buds is the amiloride-sensitive epithelial sodium channel (ENaC). However, cells and intracellular signaling underlying sodium taste in taste buds remain long-standing enigmas.

Here, we uncovered the identity of taste cells dedicated to sodium taste and the mechanisms mediating their intracellular signal transduction. First, we showed that a subset of taste cells with ENaC activity fire action potentials in response to ENaC-mediated Na⁺ influx without changing the intracellular Ca²⁺ concentration. The cells 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.

This identification of the mechanisms underlying the attractive sodium taste will help devise strategies to reduce salt consumption. The channel synapse is a new mode of chemical synapse, and it now seems to mediate all tastes but sour. The mechanisms of how this unique chemical synapse benefits gustation and contributes to other functions outside the tongue remain to be determined.

Nomura K, Nakanishi M, Ishidate F, Iwata K, Taruno A. All-Electrical Ca²⁺-Independent Signal Transduction Mediates Attractive Sodium Taste in Taste Buds. Neuron 106 (5), P816–829 (2020)
DOI: https://doi.org/10.1016/j.neuron.2020.03.006.

(Left) Schematic illustration of signal-transduction cascade in sodium cells. Note that no Ca²⁺-dependent components are involved throughout, and ENaC currentmediated steady depolarization may aid directly in the activation of CALHM1/3.
(Right) Hyper-resolution confocal images of sodium cells. Arrowheads indicate the accumulation of CALHM1 at points of contact between the cell and afferent nerves.

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¹Department of Molecular Cell PhysiologyKyoto Prefectural University of Medicine, Japan
²Japan Science and Technology Agency, PRESTO, Japan