Received January 11, 2007
Revised February 12, 2007
Accepted after revision February 28, 2007

¹ National Institute for Basic Biology

^* To whom correspondence should be addressed. E-mail: madon{at}nibb.ac.jp.

	Abstract

Dehydration causes an increase in the sodium (Na) concentration and osmolarity of body fluids. For Na homeostasis of the body, controls of Na and water intake and excretion are of prime importance. However, though the circumventricular organs (CVOs) were suggested to be involved in body-fluid homeostasis, the system for sensing Na levels within the brain, which is responsible for the control of Na- and water-intake behavior, has long been an enigma. Na_x is an atypical sodium channel that is assumed to be a descendant of the voltage-gated sodium channel family. Our studies on the Na_x-gene-targeting (Na_x ^-/-) mouse revealed that Na_x channels are localized to the CVOs and serve as a sodium-level sensor of body fluids. As the first step to understand the cellular mechanism by which the information sensed by Na_x channels is reflected in the activity of the organs, we now dissected the subcellular distribution of Na_x. Double-immunostaining and immunoelectron microscopic analyses revealed that Na_x is exclusively localized to perineuronal lamellate processes extending from ependymal cells and astrocytes in the organs. In addition, glial cells isolated from the SFO were sensitive to an increase in the extracellular sodium level, as analyzed by an ion-imaging method. These results suggest that glial cells bearing Na_x channels are the first to sense a physiological increase in the level of sodium in body fluids, and 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 salt homeostasis.

Key Words: Blood-brain barrier, Sodium channel, Ventricle

This article has been cited by other articles:

				A. S. Mecawi, A. Lepletier, I. G. Araujo, F. V. Fonseca, and L. C. Reis Oestrogenic influence on brain AT1 receptor signalling on the thirst and sodium appetite in osmotically stimulated and sodium-depleted female rats Exp Physiol, August 1, 2008; 93(8): 1002 - 1010. [Abstract] [Full Text] [PDF]

				D. Daniels, D. K. Yee, and S. J. Fluharty Hydromineral Neuroendocrinology: Angiotensin II receptor signalling Exp Physiol, May 1, 2007; 92(3): 523 - 527. [Abstract] [Full Text] [PDF]