All-Electrical Ca2+-Independent Signal Transduction Mediates Attractive Sodium Taste in Taste Buds

Neuron. 2020 Jun 3;106(5):816-829.e6. doi: 10.1016/j.neuron.2020.03.006. Epub 2020 Mar 30.

Abstract

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 Ca2+ 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 Ca2+ signals. This work also reveals ENaC-independent salt attraction.

Keywords: ATP; P2X; Salty; excitability; gustatory; mouse; neurotransmission; receptor potential; sensory; taste coding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Amiloride / pharmacology
  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Chemoreceptor Cells / metabolism
  • Chemoreceptor Cells / physiology
  • Epithelial Sodium Channel Blockers / pharmacology
  • Epithelial Sodium Channels / metabolism*
  • Mice
  • Neurons, Afferent / metabolism
  • Patch-Clamp Techniques
  • Signal Transduction / drug effects
  • Sodium / metabolism*
  • Synaptic Transmission
  • Taste / physiology*
  • Taste Buds / cytology*
  • Taste Buds / metabolism
  • Taste Buds / physiology

Substances

  • CALHM1 protein, mouse
  • Calcium Channels
  • Epithelial Sodium Channel Blockers
  • Epithelial Sodium Channels
  • Scnn1a protein, mouse
  • Scnn1b protein, mouse
  • Scnn1g protein, mouse
  • Amiloride
  • Sodium
  • Calcium