Extracellular Na+ levels regulate formation and activity of the NaX/alpha1-Na+/K+-ATPase complex in neuronal cells

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.

Channel Properties of Nax Expressed in Neurons

“…However, a very recent study reported that the immunocytochemical signals of Na x were detected in Neuro-2a cells [ 22 ]. This group postulated that Na x was expressed in neurons in the rat median preoptic nucleus (MnPO) using their antibodies [ 23 ].…”

The Role of Serum Ions Deficiencies in the Pathogenic Mechanisms of Oncological Depression – Psycho-Pharmacological Particularities

“…This risk is amplified by using anti-psychotics that prolong the QT interval [27], which is why this medication is contraindicated [12]. The pathogenic significance of hyponatremia is also linked to the disruption of sodium-potassium adenosine triphosphatase (Na + /K + -ATPase) activity, an enzyme that can cause ischemia, depression, memory and learning disorders and cognitive impairment in the brain [8,14]. This is an indirect mechanism of action of hyponatremia on neural function, with the direct mechanism being the impairment of sodium channel and pump functionality due to ionic deficiency.…”

Live-Cell Imaging of Physiologically Relevant Metal Ions Using Genetically Encoded FRET-Based Probes

“…Na + represents the most abundant extracellular cation, involved in the maintenance of the cell membrane potential [172,173]. Na + is especially important for the induction of action potentials, as it represents the first ion flowing across the membrane upon cell membrane depolarization [174].…”