Trpv4 Mediates Hypotonic Inhibition of Central Osmosensory Neurons via Taurine Gliotransmission

Cell Rep. 2018 May 22;23(8):2245-2253. doi: 10.1016/j.celrep.2018.04.090.

Abstract

The maintenance of hydromineral homeostasis requires bidirectional detection of changes in extracellular fluid osmolality by primary osmosensory neurons (ONs) in the organum vasculosum laminae terminalis (OVLT). Hypertonicity excites ONs in part through the mechanical activation of a variant transient receptor potential vanilloid-1 channel (dn-Trpv1). However, the mechanism by which local hypotonicity inhibits ONs in the OVLT remains unknown. Here, we show that hypotonicity can reduce the basal activity of dn-Trpv1 channels and hyperpolarize acutely isolated ONs. Surprisingly, we found that mice lacking dn-Trpv1 maintain normal inhibitory responses to hypotonicity when tested in situ. In the intact setting, hypotonicity inhibits ONs through a non-cell-autonomous mechanism that involves glial release of the glycine receptor agonist taurine through hypotonicity activated anion channels (HAAC) that are activated subsequent to Ca2+ influx through Trpv4 channels. Our study clarifies how Trpv4 channels contribute to the inhibition of OVLT ONs during hypotonicity in situ.

Keywords: TRPV; gliotransmission; hyptonicity; osmosensitive; swelling; taurine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Hypotonic Solutions / pharmacology*
  • Ion Channel Gating / drug effects
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Inhibition / drug effects*
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • Osmolar Concentration
  • Synaptic Transmission / drug effects*
  • TRPV Cation Channels / metabolism*
  • Taurine / pharmacology*

Substances

  • Hypotonic Solutions
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Trpv4 protein, mouse
  • Taurine
  • Calcium