Abstract
TheScn7Agene encodes NaX, an atypical noninactivating Na+channel, whose expression in sensory circumventricular organs is essential to maintain homeostatic responses for body fluid balance. However, NaXhas also been detected in homeostatic effector neurons, such as vasopressin (VP)-releasing magnocellular neurosecretory cells (MNCVP) that secrete VP (antidiuretic hormone) into the bloodstream in response to hypertonicity and hypernatremia. Yet, the physiological relevance of NaXexpression in these effector cells remains unclear. Here, we show that rat MNCVPin males and females is 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 ofScn7Aexpression. Furthermore, reducing the density of NaXchannels selectively impaired the activation of MNCVPby systemic hypernatremia without affecting their responsiveness to hypertonicityin vivo. These results identify NaXas a physiological Na+sensor, whose expression in MNCVPcontributes to the generation of homeostatic responses to hypernatremia.SIGNIFICANCE STATEMENTIn this study, we provide the first direct evidence showing that the sodium-sensing channel encoded by theScn7Agene (NaX) mediates cell-autonomous sodium detection by 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 stimulusin vitroandin vivo. These data reveal that NaXoperates as a sodium sensor in these cells and that the endogenous sensory properties of osmoregulatory effector neurons contribute to their homeostatic activationin vivo.
Funder
Gouvernement du Canada | Canadian Institutes of Health Research
IPN | Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional
McGill University Healthy Brains for Healthy Lives