Role of cerebrospinal fluid-contacting nucleus in sodium sensing and sodium appetite

The NaV1.7 Channel Subtype as an Antinociceptive Target for Spider Toxins in Adult Dorsal Root Ganglia Neurons

“…In addition and in contrast to other Na V channel subtypes, Na V 1.10 is not activated by the membrane potential but is sensitive to extracellular concentration of Na ions with a threshold value of 150 mM ( Hiyama et al, 2002 ). It is expressed in the lung, uterus and heart, in the PNS neurons (e.g., medium to large-sized DRG neurons, non-myelinating Schwann cells) and in the CNS (e.g., thalamus, hippocampus, cerebellum, median preoptic nucleus) ( Fukuoka et al, 2008 ; Garcia-Villegas et al, 2009 ) In particular, this subtype is clearly present in the primary regions implicated in hydromineral homeostasis, such as the subfornical organ, the vascular organ of the lamina terminalis and the median eminence which control the Na-intake behavior by changing neuronal excitability ( Watanabe et al, 2006 ; Xing et al, 2015 ; Kinsman et al, 2017 ). It is involved in autoimmunity process causing chronic hypernatremia ( Hiyama et al, 2010 ) and in epilectogenic process ( Gorter et al, 2010 ).…”

Connection Input Mapping and 3D Reconstruction of the Brainstem and Spinal Cord Projections to the CSF-Contacting Nucleus

“…The study of this nucleus is about 30 years after we discovered and named this nucleus. The basic biological characteristics of the CSF-contacting nucleus such as specific labeling method (Lu et al, 2008), location and stereotaxic coordinates (Song et al, 2019), receptor, neurotransmitter, and ion channel distributions (Lu et al, 2011;Wang et al, 2014;Liu et al, 2017), and their relationships with morphine dependence and withdrawal, stress, sodium appetite, and pain (Lu et al, 2011;Wu et al, 2015;Xing et al, 2015;Zhou et al, 2017) have been revealed. However, the pathways and mechanisms associated with such biological activities have not been elucidated yet.…”

“…The CSF-contacting nucleus is also located in the brainstem and participates in pain and other behaviors (Lu et al, 2011;Xing et al, 2015;Liu et al, 2017). To demonstrate the functions and neural networks of the CSF-contacting nucleus in the central nervous system, it is import to identify the existence of connections from the brainstem and spinal cord to the CSF-contacting nucleus and to elucidate the connections from different functional regions.…”

Na+ homeostasis by epithelial Na+ channel (ENaC) and Nax channel (Nax): cooperation of ENaC and Nax

“…Thus, the low GFR due to a decrease in the circulating blood caused by low body Na + content increases renin release, leading to elevation of body Na + content due to an increase in Na + reabsorption via aldosterone-induced increases of ENaC production and surface expression in the collecting duct. Further, recently Na x has been reported to be a Na + concentration-sensitive Na + channel acting as a Na + sensor (46)(47)(48)(49)(50)(51)(52)(53)60,61). Na x was found in the brain as an atypical Na + channel, poorly homologous to the voltage-gated Na + channels (62).…”

“…Further, the linkage between detection of high ECF Na + concentration via Na x and water intake is mediated by TRPV4 (51): knock-out of TRPV4 in mice induces no water intake even at high Na + concentration in cerebrospinal fluid (CSF) (51), in which CSF-contacting nucleus (CSF-CN) plays an important role in sensing the Na + concentration of CSF and satiating Na + appetite (53). Na x has the cation selectivity of Na + ≈ Li + > Rb + > Cs + and is bound to postsynaptic density protein 95 (PSD95) via its PSD95/Disc-large/ZO-1 (PDZ)-binding motif at the C-terminus in neurons, suggesting involvement of this complex in the surface expression of Na x (49).…”