Na X channel is a physiological [Na + ] detector in oxytocin and vasopressin releasing magnocellular neurosecretory cells of the rat supraoptic nucleus.

The Scn7A gene encodes Na X , an atypical non-inactivating Na + channel whose expression in sensory circumventricular organs is essential to maintain homeostatic responses for body fluid balance. However, Na X has also been detected in homeostatic effector neurons, such as vasopressin (VP) releasing magnocellular neurosecretory cells (MNC VP ) which secrete VP (antidiuretic hormone) into the bloodstream in response to hypertonicity and hypernatremia. Yet, the physiological relevance of Na X expression in these effector cells remains unclear. Here we show that rat MNC VP in males and females are depolarized and excited in proportion with isosmotic increases in [Na + ]. These responses were caused by an inward current resulting from a cell-autonomous increase in Na + conductance. The Na + -evoked current was unaffected by blockers of other Na + -permeable ion channels but was significantly reduced by shRNA-mediated knockdown of Scn7A expression. Furthermore, reducing the density of Na X channels selectively impaired the activation of MNC VP by systemic hypernatremia without affecting their responsiveness to hypertonicity in vivo These results identify Na X as a physiological Na + sensor whose expression in MNC VP contributes to the generation of homeostatic responses to hypernatremia. Significance Statement In this study, we provide the first direct evidence showing that the sodium-sensing channel encoded by the Scn7A gene (Na X ) mediates cell-autonomous sodium detection by magnocellular neurosecretory cells (MNCs) in the low millimolar range and that selectively reducing the expression of these channels in MNCs, impairs their activation in response to a physiologically relevant sodium stimulus in vitro and in vivo These data reveal that Na X operates as a sodium sensor in these cells and that the endogenous sensory properties of osmoregulatory effector neurons contribute to their homeostatic activation in vivo .