The subfornical organ, a specialized sodium channel, and the sensing of sodium levels in the brain

Dehydration causes an increase in the sodium (Na) concentration and osmolarity of body fluid. For Na homeostasis of the body, controls of Na and water intake and excretion are of prime importance. However, though the circumventricular organs (CVOs) are suggested to be involved in body-fluid homeostasis, the system for sensing the Na level within the brain that is responsible for the control of Na- and water-intake behavior has long been an enigma. The authors found that the Na-x channel is preferentially expressed in the CVOs in the brain and that Na-x knockout mice ingest saline in excess under dehydrated conditions. Subsequently, the authors demonstrated that Na-x is an Na-level-sensitive Na channel. When Na-x cDNA was introduced into the brain of the knockout mice with an adenoviral expression vector, only animals that received a transduction of the Nax gene into the subfornical organ (SFO) among the CVOs recovered salt-avoiding behavior under dehydrated conditions. Here, the authors advocate that the SFO is the center of the control of salt-intake behavior in the brain, where the Na-level-sensitive Na-x channel is involved in sensing the physiological increase in the level of Na in body fluids.