Salt homeostasis is essential to survival, but brain mechanisms for salt-intake control have not been fully elucidated. Here, we found that the sensitivity of Nax channels to [Na+]o is dose-dependently enhanced by endothelin-3 (ET-3). Nax channels began to open when [Na+]o exceeded ∼150 mM without ET-3, but opened fully at a physiological [Na+]o (135-145 mM) with 1 nM ET-3. Importantly, ET-3 was expressed in the subfornical organ (SFO) along with Nax, and the level was robustly increased by dehydration. Pharmacological experiments revealed that endothelin receptor B (ET BR) signaling is involved in this modulation of Nax gating through protein kinase C and ERK1/2 activation. ETBR agonists increased the firing rate of GABAergic neurons via lactate in the SFO, and an ETBR antagonist attenuated salt aversion during dehydration. These results indicate that ET-3 expression in the SFO is tightly coupled with body-fluid homeostasis through modulation of the [Na+]o sensitivity of Nax.
|Number of pages||13|
|Publication status||Published - Apr 2 2013|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology