Abstract
Dehydration causes an increase in the sodium (Na) concentration and osmolarity of body fluid. For Na homeostasis of the body, controls of Na/water-intake and -excretion are of prime importance. However, the system for sensing the Na level within the brain that is responsible for the control of Na/water-intake behavior remains to be elucidated. Using physiological and behavioral techniques in combination with genetic manipulations, we have demonstrated that a sodium channel Nax is indispensable for the Na-level-sensing in the brain. We previously showed that Nax channel is preferentially expressed in glial cells in the circumventricular organs (CVOs) and that Nax-knockout mice ingest saline in excess under dehydrated conditions. Subsequently, we demonstrated that Nax is a Na-level-sensitive Na channel. Recently, we confirmed the physiological role of the Nax in vivo by infusion of hypertonic Na solution to the cerebral ventricle. The infusion induced prompt intake of water and aversion to salt in wild-type mice. In contrast, such aversive behavior was not observed in the knockout mice. When Nax cDNA was introduced into the brain of the knockout mice with an adenoviral expression vector, only animals with a transduction of the Nax gene into the subfornical organ (SFO) among the CVOs recovered salt-avoiding behavior under dehydrated conditions. These results clearly indicate that the SFO is the center of the control of salt-intake behavior in the brain, where the Na-level-sensitive Nax channel is involved in sensing the physiological increase in the Na level of body fluids. [J Physiol Sci. 2006;56 Suppl:S38]
