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Compartmentalization of hypothalamic TRPV4 in lipid rafts in the rat: putative role in the central control of body fluid homeostasis
Author(s) -
Carreno Flavia R.,
Ji Lisa L.,
Cunningham J. Thomas
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1406-a
Subject(s) - trpv4 , compartmentalization (fire protection) , medicine , endocrinology , hypothalamus , lipid raft , homeostasis , microbiology and biotechnology , chemistry , intracellular , forebrain , osmoregulation , biology , transient receptor potential channel , receptor , central nervous system , cholesterol , biochemistry , enzyme , ecology , salinity
The molecular mechanisms underlying the osmotic sensitivity of hypothalamic neurons have not been fully described. Recent studies indicate that transient receptor potential (TRP) channels contribute to the intrinsic osmosensitivity of cells from the supraoptic nucleus (SON) and other osmotically sensitive parts of the forebrain. The impaired osmotic regulation in trpv4 − / − mice suggests TRPV4 plays a role in osmotic signaling. Using different models of dehydration and bile duct ligations (BDL), a model of hepatic cirrhosis associated with elevated circulating vasopressin with hypo‐osmolality, we tested the hypothesis that TRPV4 expression (western blotting) and compartmentalization could be regulated by changes in plasma osmolality. We found increased expression of TRPV4 in SON of 48 h water deprived rats and also in rats given 2% saline to drink for 10 days. The abundance of TRPV4 and nNOS was increased in the SON of BDL rats. Next we hypothesized that compartmentalization of the TRPV4 in the plasma membrane may play a role in its signaling. We have found that TRPV4 associates with lipid rafts (LR) in hypothalamus membranes (HM) from normal rats and a higher abundance of TRPV4 was associated in LR of BDL rats HM. When BDL rats were given 0.9% saline to drink, the abundance of TRPV4 associated with LR in HM returned to the control levels. In conclusion, our data suggest that changes in the expression and compartmentalization of TRPV4 in lipid rafts could alter the intracellular signaling of magnocellular neurons. (NIH HL062579 & DK57822).