Trpv4 Mediates Hypotonic Inhibition of Central Osmosensory Neurons via Taurine Gliotransmission

Publication date: 22 May 2018
Source:Cell Reports, Volume 23, Issue 8
Author(s): Sorana Ciura, Masha Prager-Khoutorsky, Zahra S. Thirouin, Joshua C. Wyrosdic, James E. Olson, Wolfgang Liedtke, Charles W. Bourque
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.

Graphical abstract

Teaser

Ciura et al. show that osmosensory neurons in organum vasculosum lamina terminalis are inhibited by hypotonicity. This effect is triggered by activation of Trpv4 channels and Ca²⁺ accumulation in astrocytes, causing these cells to release taurine through anion channels. Taurine inhibits firing by activating glycine receptors on the osmosensory neurons.


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