Nav2/NaG channel is involved in control of salt-intake behavior in the CNS

Nav2/NaG is a putative sodium channel, whose physiological role has long been an enigma. We generatedNav2gene-deficient mice by inserting thelacZgene. Analysis of the targeted mice allowed us to identify Nav2-producing cells by examining thelacZexpression. Besides in the lung, heart, dorsal root ganglia, and Schwann cells in the peripheral nervous system,Nav2was expressed in neurons and ependymal cells in restricted areas of the CNS, particularly in the circumventricular organs, which are involved in body-fluid homeostasis. Under water-depleted conditions,c-fosexpression was markedly elevated in neurons in the subfornical organ and organum vasculosum laminae terminalis compared with wild-type animals, suggesting a hyperactive state in theNav2-null mice. Moreover, the null mutants showed abnormal intakes of hypertonic saline under both water- and salt-depleted conditions. These findings suggest that the Nav2 channel plays an important role in the central sensing of body-fluid sodium level and regulation of salt intake behavior.