null New understanding of the physiological response to dehydration and salt intake

An RI-MUHC research team has uncovered the mechanism that leads to the release of the antidiuretic hormone vasopressin


In a new study published in the Journal of Neuroscience, scientists at the Research Institute of the McGill University Health Centre (RI-MUHC) have revealed that an ion channel protein called NaX functions as a physiological sodium sensor in the neurons that release the antidiuretic hormone vasopressin.

A team led by Charles Bourque, PhD, of the Brain Repair and Integrative Neuroscience (BRaIN) Program, has discovered that the NaX protein causes an electrical excitation of these vasopressin releasing neurons when the blood concentration of sodium ions is increased. An increase in sodium concentration in blood occurs during dehydration, or after ingesting a significant amount of sodium. The excitation of vasopressin releasing neurons caused by NaX under these conditions instructs the kidney to conserve water as a key homeostatic response.

“Although sodium-mediated release of vasopressin is a well-established physiological response, the mechanism by which this actually occurs was unclear,” says Professor Bourque. “Previous work had shown that the NaX protein can operate as a sodium sensor in other parts of the brain. In this study, we wanted to find out if the NaX channel protein was expressed in vasopressin-releasing neurosecretory cells of the supraoptic nucleus, and if it played a role in mediating their electrical excitation in response to an increase in extracellular sodium concentration.”

Vasopressin is secreted when blood sodium concentration rises. After a salty meal, or a sweaty workout, vasopressin is key to maintaining fluid electrolyte balance in the body. It promotes water reabsorption by the kidney, which in turn dilutes and equilibrates the blood sodium concentration to maintain blood osmolality in the desired range. This vital physiological response, known as osmoregulation, can be upset by the release of too much vasopressin, which can lead to increased blood pressure and even sodium-dependent hypertension.

“In this study, we showed that the NaX protein is expressed by vasopressin neurons,” says Sandra Salgado-Mozo, first author of the publication and a PhD student in Professor Bourque’s lab at the time of this study. “We also showed that the NaX protein plays a key role in mediating the excitation of these cells when there is an increase in sodium concentration in the blood.”

The results of the study reveal not only how NaX channel operates as a sodium sensor in vasopressin neurons, but also that the endogenous sensory properties of these neurons contribute to their homeostatic activation in vivo.

“Going forward, further research must verify the role of the NaX channel protein in humans,” adds Prof. Bourque. “We anticipate that our work will be of interest to researchers and clinicians interested in fluid electrolyte balance and the causes of hypertension, particularly sodium-dependent hypertension.”

Left image shows vasopressin releasing neurons (magenta) and nuclei of neurons activated by an increase in blood sodium (cyan). Sandra Salgado-Mozo (centre) is the first author of the study led by Charles Bourque (right).
Left image shows vasopressin releasing neurons (magenta) and nuclei of neurons activated by an increase in blood sodium (cyan). Sandra Salgado-Mozo (centre) is the first author of the study led by Charles Bourque (right).

November 15, 2023

About the study

Read the publication: NaX channel is a physiological [Na+] detector in oxytocin and vasopressin releasing magnocellular neurosecretory cells of the rat supraoptic nucleus in the Journal of Neuroscience. First published 2 October 2023 by Sandra Salgado-Mozo, Zahra S. Thirouin, Joshua C. Wyrosdic, Ubaldo García-Hernández and Charles W. Bourque.

The authors gratefully acknowledge funding from the Canadian Institutes of Health Research and pre-clinical services support from the Animal Resources Division at the RI-MUHC.

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