title: 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.
authors.affiliation: Centre de Recherche du CHU de Québec, Axe Neurosciences QC, Canada.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Berret
authors.affiliation: Centre de Recherche du CHU de Québec, Axe Neurosciences QC, Canada.
authors.forename: Pascal Y
authors.initials: PY
authors.lastname: Smith
authors.affiliation: Centre de Recherche du CHU de Québec, Axe Neurosciences QC, Canada.
authors.forename: Mélaine
authors.initials: M
authors.lastname: Henry
authors.affiliation: Centre de Recherche du CHU de Québec, Axe Neurosciences QC, Canada ; Faculté de Médecine, Département de Psychiatrie et Neurosciences, Université Laval QC, Canada.
authors.forename: Denis
authors.initials: D
authors.lastname: Soulet
authors.affiliation: Centre de Recherche du CHU de Québec, Axe Neurosciences QC, Canada ; Faculté de Médecine, Département de Psychiatrie et Neurosciences, Université Laval QC, Canada.
authors.forename: Sébastien S
authors.initials: SS
authors.lastname: Hébert
authors.affiliation: Faculté de Médecine, Département de Psychiatrie et Neurosciences, Université Laval QC, Canada ; Institut Universitaire de Santé Mentale de Québec, Université Laval QC, Canada.
authors.forename: Katalin
authors.initials: K
authors.lastname: Toth
authors.affiliation: Centre de Recherche du CHU de Québec, Axe Neurosciences QC, Canada ; Institut Universitaire de Santé Mentale de Québec, Université Laval QC, Canada.
authors.forename: Didier
authors.initials: D
authors.lastname: Mouginot
authors.affiliation: Centre de Recherche du CHU de Québec, Axe Neurosciences QC, Canada ; Faculté de Médecine, Département de Psychiatrie et Neurosciences, Université Laval QC, Canada.
authors.forename: Guy
authors.initials: G
authors.lastname: Drolet
keywords: Na+/K+-ATPase; NaX channel; median preoptic nucleus; salt diet; sodium