Regulation of Central Na+ Detection Requires the Cooperative Action of the NaX Channel and alpha 1 Isoform of Na+/K+-ATPase in the Na+-Sensor Neuronal Population

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, NaX. 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 alpha 1 and alpha 3 isoforms of Na+/K+-ATPase, ouabain or strophanthidin, inhibited this Na+ current. However, strophanthidin, which selectively blocks the alpha 1 isoform, was more effective in blocking Na+ current, suggesting that the Na+/K+-ATPase- alpha 1 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 NaX channel decreased significantly. Our results suggest that Na+/K+-ATPase interacts with the NaX 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 alpha 1 isoform of Na+/K+-ATPase acts as a direct regulatory partner of the NaX channel and influences Na+ influx via controlling the Na+ permeability of the channel.