Abstract
MnPO neurons play a critical role in hydromineral homeostasis regulation by acting as sensors of extracellular sodium concentration ([Na+]out). The mechanism underlying Na+-sensing involves Na+-flow through the NaX channel, directly regulated by the Na+/K+-ATPase α1-isoform which controls Na+-influx by modulating channel permeability. Together, these two partners form a complex involved in the regulation of intracellular sodium ([Na+]in). Here we aim to determine whether environmental changes in Na+ could actively modulate the NaX/Na+/K+-ATPase complex activity. We investigated the complex activity using patch-clamp recordings from rat MnPO neurons and Neuro2a cells. When the rats were fed with a high-salt-diet, or the [Na+] in the culture medium was increased, the activity of the complex was up-regulated. In contrast, drop in environmental [Na+] decreased the activity of the complex. Interestingly under hypernatremic condition, the colocalization rate and protein level of both partners were up-regulated. Under hyponatremic condition, only NaX protein expression was increased and the level of NaX/Na+/K+-ATPase remained unaltered. This unbalance between NaX and Na+/K+-ATPase pump proportion would induce a bigger portion of Na+/K+-ATPase-control-free NaX channel. Thus, we suggest that hypernatremic environment increases NaX/Na+/K+-ATPase α1-isoform activity by increasing the number of both partners and their colocalization rate, whereas hyponatremic environment down-regulates complex activity via a decrease in the relative number of NaX channels controlled by the pump.
Highlights
Sodium (Na+) and sodium chloride (NaCl) is the most abundant extracellular electrolyte and the major determinant of osmolarity
CHANGES IN SYSTEMIC Na+ INFLUENCE NaX/Na+/K+-ATPASE α-1 COMPLEX ACTIVITY IN median preoptic nucleus (MnPO) NEURONS We first aimed to determine how changes in Na+ intake could influence the activity of the NaX/Na+/K+-ATPase α-1 complex in MnPO neurons
The present study proposes a novel mechanism of how changes in extracellular [Na+] may contribute to the regulation of sodium homeostasis
Summary
Sodium (Na+) and sodium chloride (NaCl) is the most abundant extracellular electrolyte and the major determinant of osmolarity. It has been proposed that extracellular sodium ([Na+]out) variations are measured mainly by an atypical sodium channel, namely NaX, a recognized Na+-sensor (Hiyama et al, 2002, 2004; Grob et al., 2004; Noda, 2006). NaX channel is a Na+ leak channel allowing Na+ ions to pass through the membrane, and detect local variations in [Na+]out (Tremblay et al, 2011). Previous study described a direct interaction between the NaX channel and the Na+/K+-ATPase pump in astrocytes located in the CVOs in mice (Shimizu et al, 2007). We demonstrated that NaX channel is directly regulated by α-1 isoform of the Na+/K+-ATPase, forming a functional complex located close to the cell membrane and plays an important role in the regulation of local [Na+] (Berret et al, 2013). The mechanism by which other factors modulate the activity of this functional complex remains unknown
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