title: Regulation of central Na+ detection requires the cooperative action of the NaX channel and α1 Isoform of Na+/K+-ATPase in the Na+-sensor neuronal population.
abstract: The median preoptic nucleus (MnPO) holds a strategic position in the hypothalamus. It is adjacent to the third ventricle; hence, it can directly access the ionic composition of the CSF. MnPO neurons play a critical role in hydromineral homeostasis regulation by acting as central sensors of extracellular Na(+) concentration ([Na(+)](ext)). The mechanism underlying Na(+) sensing involves the atypical Na(+) channel, Na(X). Here we sought to determine whether Na(+) influx in Na(+) sensors is actively regulated via interaction with other membrane proteins involved in cellular Na(+) homeostasis, such as Na(+)/K(+)-ATPase. The Na(+)/K(+)-ATPase role was investigated using patch-clamp recordings in rat MnPO dissociated neurons. Na(+) current evoked with hypernatriuric solution was diminished in the absence of ATP/GTP, indicating that Na(+)/K(+)-ATPase play a central role in [Na(+)](ext) detection. Specific blockers of α1 and α3 isoforms of Na(+)/K(+)-ATPase, ouabain or strophanthidin, inhibited this Na(+) current. However, strophanthidin, which selectively blocks the α1 isoform, was more effective in blocking Na(+) current, suggesting that the Na(+)/K(+)-ATPase-α1 isoform is specifically involved in [Na(+)](ext) detection. Although strophanthidin did not alter either the membrane resistance or the Na(+) reversal potential, the conductance and the permeability of the Na(X) channel decreased significantly. Our results suggest that Na(+)/K(+)-ATPase interacts with the Na(X) channel and regulates the high [Na(+)](ext)-evoked Na(+) current via influencing the Na(+) influx rate. This study describes a novel intracellular regulatory pathway of [Na(+)](ext) detection in MnPO neurons. The α1 isoform of Na(+)/K(+)-ATPase acts as a direct regulatory partner of the Na(X) channel and influences Na(+) influx via controlling the Na(+) permeability of the channel.
authors: Axe Neurosciences du Centre de Recherche du Centre Hospitalier Université de Québec (CHUQ), Université Laval, Québec, QC, Canada G1V 4G2.
authors: Emmanuelle
authors: E
authors: Berret
authors: Benjamin
authors: B
authors: Nehmé
authors: Mélaine
authors: M
authors: Henry
authors: Katalin
authors: K
authors: Toth
authors: Guy
authors: G
authors: Drolet
authors: Didier
authors: D
authors: Mouginot
mesh_terms: D000465:Algorithms; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010539:Permeability; D011301:Preoptic Area / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013327:Strophanthidin / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D010042:Ouabain; D013327:Strophanthidin; D012964:Sodium; C499075:Atp1a1 protein, rat; D000254:Sodium-Potassium-Exchanging ATPase