Fasting regulates expression of voltage-gated Na+ channel Nav1.3 in subfornical organ

The subfornical organ (SFO) is a sensory circumventricular organ of the central nervous system and plays a key role in regulation of a number of homeostatic processes because of its ability to detect and respond to circulating signals and communication to homeostatic control centres. A previous study reported a change in expression of 687 transcripts in rat SFO following a 48h fast; of particular interest was the observed downregulation of the transcript encoding the Nav1.3 voltage-gated Na+ channel. Therefore, we carried out a study to examine the effects of a 48h fast on electrical properties of SFO neurons. First, we carried out an immunohistochemical analysis of rat SFO to confirm expression of Nav1.3 protein. Next, we carried out qPCR analysis of mRNA from SFO of sated rats and 48h fasted rats and confirm that a 48hr fast caused a downregulation of Nav1.3. Using patch clamp analysis of SFO neurons acutely isolated from rats following a 48h fast, a statistically significant decrease in peak Na+ current density, as well as shifts in voltage dependence of activation and inactivation, and a slowing to time dependent recovery from inactivation were observed. These changes were accompanied by a depolarization of the threshold to fire action potentials and a decrease in frequency of spontaneous action potentials. Together, these data show that the electrical properties of SFO neurons are altered by a 48hr fast, indicating SFO is a dynamic sensor of circulating signals. •The subfornical organ (SFO) of the brain lacks a blood brain barrier.•SFO neurons detect important circulating signals for regulation of homeostasis.•48h fast downregulates expression of mRNA encoding Nav1.3 voltage-gated Na + channels.•Downregulation of Nav1.3 reduces Na + current amplitude.•Downregulation of Nav1.3 reduces excitability of SFO neurons.