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Société de Neuroendocrinologie

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Central mechanisms of osmosensation and systemic osmoregulation

Chales W Bourque
McGill University, Montreal, Canada

Systemic osmoregulation is a homeostatic process of vital importance and the endocrine (e.g. vasopressin release) and behavioral responses (e.g. thirst) that mediate this process are controlled in large part by osmosensory neurons located within the brain. Notably, neurons in the organum vasuclosum lamina terminalis (OVLT) and vasopressin-releasing neurons in the supraoptic nucleus (SON) display a cell-autonomous response to hypertonicity whereby shrinking induces an increase in non-selective cation conductance. This effect causes a membrane depolarization and contributes to the excitation of OVLT and SON neurons that mediate thirst and vasopressin secretion. The molecular identity of the osmoreceptor channel is not known, but appears to involve a capsaicin-insensitive variant of the transient receptor potential vanilloid type 1 (Trpv1) channel that lacks amino acids located in the amino terminus of the protein (ΔN-Trpv1; Ciura and Bourque, 2006; Sharif-Naeini et al, 2006). We thus isolated high quality mRNA from OVLTs and SONs dissected from 52 rats (with other tissues) and reversed transcribed this material into cDNA using oligo-DT primers. Probing this material by Polymerase chain reaction (PCR) with specific primers we identified a 2 kb amplicon whose size was consistent with that expected of a defined ΔN-terminal variant. Sequencing analysis identified the complete nucleotide sequence of the variant, providing important information concerning its secondary structure. Moreover, specific primers verified the expression of this specific variant by RT-PCR in single OVLT and SON neurons. Heterologous expression of ΔN-Trpv1 by transfection into human embryonic kidney (HEK293) cells and cultured hypothalamic neurons obtained from Trpv1 knockout mice, conferred osmosensory characteristics similar to those of SON and OVLT neurons. These results suggest that ΔN-Trpv1 operates as an osmoreceptor in SON and OVLT neurons. However the osmotic regulation of osmosensory neurons and vasopressin release is not completely abolished in situ in Trpv1 knockout mice. Results indicating that glial cells also contribute to central osmosensation will be presented.

This work was supported by CIHR grants FNF-82818 & MOP-9939, and a James McGill Research Chair.

Keyword(s): vasopressine, osmoregulation, supraoptique