SPEAKER Participation of osmo and sodiumsensitive channels in the control of body sodium depletion responses.

A. GODINO

Simposio; Using Modern Molecular Tools for the Study of Integrative and Translational Physiology; 2019

Changes in body water/sodium balance are tightly controlled by central and peripheral osmo?sodium receptors among others, which trigger the activity of a central network that mainly release vasopressin and/or angiotensin/aldosterone, increase renal sympathetic nerve activity, and induce thirst and sodium appetite. The main central sodium-osmoreceptive cells are in the circumventricular organs of the lamina terminalis, i.e. the organum vasculosum of the lamina terminalis (OVLT), the subfornical organ (SFO) and along the hypothalamic magnocellular cells. It has been postulated that their intrinsic osmosensitivity is mediated in part by different types of channels, TRPV1, TRPV4, NaX and EnaC, among others. The function of TRPV1/TRPV4 channels have been previously analyzed using knockout (KO) mice; however their functional role after different types of hyperosmotic thirst remains controversial (Ciura and Bourque 2006; Kinsman et al., 2014) and their participation in sodium appetite (SA) behavior and renal responses during a body sodium depletion (SD) has not been deeply analyzed yet. Our present work focus on the TRPV1, TRPV4 and NaX channels involvement in the genesis of the SA induced by SD. We will discuss our evidence showing, in vivo and in vitro, changes in the central expression of TRPV1 at different times after body sodium depletion or after angiotensin II stimulation respectively. We deep further this analysis using the TRPV1 KO model where we evaluated the channel involvement in the behavioral and renal responses at different times after body sodium depletion. After SD, the KO animals showed an increase in the sodium preference since they consumed a higher hypertonic cocktail in relation to WT animals, independent of the time after SD. Finally, we also debate our data regarding the temporal changes in gene expression channels (NaX and TRPV4) after SD in wild type mice along the SFO and OVLT and in comparison to TRPV1 KO animals.In summary, our results indicate that the TRPV1/TRPV4/NaX channels have a temporal pattern of expression after SD, modulating behavioral and renal compensatory responses to reestablish the hydroelectrolyte homeostasis.