An N-terminal variant of Trpv1 channel is required for osmosensory transduction.
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.
Sharif Naeini
Reza
R
Centre for Research in Neuroscience, McGill University, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada.
Witty
Marie-France
MF
Séguéla
Philippe
P
Bourque
Charles W
CW
D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood / Q000378:metabolism; D048429:Cell Size; D004594:Electrophysiology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012677:Sensation / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013495:Supraoptic Nucleus / Q000166:cytology / Q000502:physiology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology*; D014882:Water-Electrolyte Balance / Q000502:physiology*
D009479:Neuropeptides; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D001127:Arginine Vasopressin