Sodium-level-sensitive sodium channel Na_x is expressed in glial laminate processes in the sensory circumventricular organs

Abstract

Na(x) is an atypical sodium channel that is assumed to be a descendant of the voltage-gated sodium channel family. Our recent studies on the Na(x)-gene-targeting mouse revealed that Na(x) channel is localized to the circumventricular organs (CVOs), the central loci for the salt and water homeostasis in mammals, where the Na(x) channel serves as a sodium-level sensor of the body fluid. To understand the cellular mechanism by which the information sensed by Na(x) channels is transferred to the activity of the organs, we dissected the subcellular localization of Na(x) in the present study. Double-immunostaining and immunoelectron microscopic analyses revealed that Na(x) is exclusively localized to perineuronal lamellate processes extended from ependymal cells and astrocytes in the organs. In addition, glial cells isolated from the subfornical organ, one of the CVOs, were sensitive to an increase in the extracellular sodium level, as analyzed by an ion-imaging method. These results suggest that glial cells bearing the Na(x) channel are the first to sense a physiological increase in the level of sodium in the body fluid, and they regulate the neural activity of the CVOs by enveloping neurons. Close communication between inexcitable glial cells and excitable neural cells thus appears to be the basis of the central control of the salt homeostasis.

Distinct neural mechanisms for the control of thirst and salt appetite in the subfornical organ

“…I.2A; Goldin et al, 2000). elevations in body fluids within the physiological range (Hiyama et al, 2002;Noda and Hiyama, 2005;Noda, 2006;Watanabe et al, 2006;Noda and Sakuta, 2013;Noda and Hiyama, 2015a;Noda and Hiyama, 2015b). The sensitivity of Na x to [Na + ] was revealed to be upregulated by endothelin-3 through activation of endothelin receptor B (Hiyama et al, 2013).…”

Potential New Antiepileptogenic Targets Indicated by Microarray Analysis in a Rat Model for Temporal Lobe Epilepsy

“…Other genes that are expressed in glial cells are related to water and ion homeostasis (Simard and Nedergaard, 2004). A gene that was persistently upregulated was the Scn6a, an atypical sodium channel gene that serves as a sodium-level sensor of the body fluid (Hiyama et al, 2002;Watanabe et al, 2006). This gene was originally considered to be a glial sodium channel (Gautron et al, 1992), although neuronal localization has also been observed (Grob et al, 2004).…”

Neuronal Sodium Leak Channel Is Responsible for the Detection of Sodium in the Rat Median Preoptic Nucleus

“…The existence of specific cerebral Na ϩ sensors for the detection and correction of hydromineral imbalance has long been hypothesized (Andersson et al 1975;Cox et al 1987;Olsson and Kolmodin 1974;Weisinger et al 1979), and a concentration-sensitive Na ϩ channel, called the Na X channel, has been reported to control sodium ingestion in mice (Noda 2006;Watanabe et al 2000). In these rodents, the Na X channel is specifically expressed by glial cells of the circumventricular organs (Watanabe et al 2006). In addition, the transduction of the ECF [Na ϩ ] (Ͼ150 mM) into neuronal action potentials involves a complex mechanism and results in part from lactate release by glial cells under hypernatriuric conditions (Shimizu et al 2007).…”