An N-terminal variant of Trpv1 channel is required for osmosensory transduction

Nat Neurosci. 2006 Jan;9(1):93-8. doi: 10.1038/nn1614. Epub 2005 Dec 4.


Body fluid homeostasis requires the release of arginine-vasopressin (AVP, an antidiuretic hormone) from the neurohypophysis. This release is controlled by specific and highly sensitive 'osmoreceptors' in the hypothalamus. Indeed, AVP-releasing neurons in the supraoptic nucleus (SON) are directly osmosensitive, and this osmosensitivity is mediated by stretch-inhibited cation channels. However, the molecular nature of these channels remains unknown. Here we show that SON neurons express an N-terminal splice variant of the transient receptor potential vanilloid type-1 (Trpv1), also known as the capsaicin receptor, but not full-length Trpv1. Unlike their wild-type counterparts, SON neurons in Trpv1 knockout (Trpv1(-/-)) mice could not generate ruthenium red-sensitive increases in membrane conductance and depolarizing potentials in response to hyperosmotic stimulation. Moreover, Trpv1(-/-) mice showed a pronounced serum hyperosmolality under basal conditions and severely compromised AVP responses to osmotic stimulation in vivo. These results suggest that the Trpv1 gene may encode a central component of the osmoreceptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine Vasopressin / blood
  • Arginine Vasopressin / metabolism
  • Cell Size
  • Electrophysiology
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / physiology*
  • Neuropeptides / physiology
  • Paraventricular Hypothalamic Nucleus / cytology
  • Paraventricular Hypothalamic Nucleus / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensation / physiology*
  • Signal Transduction / physiology*
  • Supraoptic Nucleus / cytology
  • Supraoptic Nucleus / physiology
  • TRPV Cation Channels / antagonists & inhibitors
  • TRPV Cation Channels / genetics*
  • TRPV Cation Channels / physiology*
  • Water-Electrolyte Balance / physiology*


  • Neuropeptides
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Arginine Vasopressin