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

Nature Neurosciencevolume 9pages9398 (2006) | Download Citation



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.

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We thank H. Gainer (US National Institute of Neurological Disorders and Stroke) for supplying the anti-AVP antibodies used in this study. We thank also S.H. Oliet, T. Stachniak, Z. Zhang, S. Ciura and E. Trudel for advice during the preparation of the manuscript. This work was supported by operating grants from the Canadian Institutes of Health Research (CIHR) to C.W.B. and P.S. Additional support was provided to C.W.B. through a CIHR Senior Investigator Award and a James McGill Research Chair. R.S.N. is a recipient of a CIHR Doctoral Award. P.S. is a Killam scholar.

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  1. Centre for Research in Neuroscience, McGill University, 1650 Cedar Avenue, Montreal, H3G 1A4, Quebec, Canada

    • Reza Sharif Naeini
    •  & Charles W Bourque
  2. Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, H3A 2B4, Quebec, Canada

    • Marie-France Witty
    •  & Philippe Séguéla


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The authors declare no competing financial interests.

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Correspondence to Charles W Bourque.

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