Interaction between angiotensin II and glucose sensing at the subfornical organ.

The subfornical organ (SFO) lacks the normal blood brain barrier and senses the concentrations of many different circulating signals including glucose and angiotensin II (ANG II). ANG II has recently been implicated in the control of food intake and body weight gain. The present study assessed whether single SFO neurons sense changes in glucose and ANG II, and if changes in glucose concentration alters these neurons responsiveness to ANG II. SFO neurons dissociated from male Sprague-Dawley rats (100-175g) were used. We first examined if glucose concentration modulates AT1 receptor expression, and found similar AT1a mRNA expression levels at 1mM, 5mM and 10mM glucose concentrations in dissociated SFO neurons. Glucose responsiveness of SFO neurons were assessed using perforated current-clamp recordings and switching between 5mM and 10mM glucose artificial cerebrospinal fluid (aCSF) to classify single neurons as non-responsive (nGS), glucose-excited (GE) or glucose-inhibited (GI). A total of 26.7% of the SFO neurons were GI (n=24/90), 21.1% were GE (n=19/90) and 52.2% were nGS (n=47/90). Once classified the effects of 10nM ANG II on the excitability of these neurons was then tested and 52% of GE (n=10/19), 71% in GI 71% (n=17/24) and 43% in nGS (n=20/47) neurons were ANG II sensitive. Finally, we tested if acute changes in glucose concentration modified the response to ANG II and showed that some neurons (4/17) only respond to ANG II at 10 mM glucose. Our data demonstrates that the same SFO neuron can sense glucose and ANG II and that acute changes in glucose concentration may change ANG II responsiveness. This article is protected by copyright. All rights reserved.