Regulation of Brain Na-K ATPase Activity by Noradrenaline with Particular Reference to Normal and Altered Rapid Eye Movement Sleep

Abstract

Rapid eye movement sleep (REMS) is naturally expressed at least in all the mammals, including humans, studied so far. It is regulated by interplay among complex neuronal circuitry in the brain involving various neurotransmitters. Although the precise function and role of REMS is yet to be deciphered, loss of REMS increases brain excitability; however, the mechanism of action was unknown. As Na-K ATPase is the key molecule that maintains ionic homeostasis across neuronal membrane and modulates the excitability status of neurons, we proposed that REMS deprivation (REMSD) could affect the neuronal Na-K ATPase activity. On the other hand, evidences suggest that REMSD would elevate noradrenaline (NA) level in the brain and it has been proposed that REMS maintains brain NA at an optimum level. Therefore, while attempting to understand and explain the mechanism of action we hypothesized that REMSD-induced elevated NA could modulate Na-K ATPase activity in the brain and thus modulates the neuronal and brain excitability. In this chapter first we discuss the mechanism of increase in NA level in the brain after REMSD. Then we discuss the effect of such elevated NA on neuronal and glial Na-K ATPase activity. We observed that REMSD-induced increase in NA affected neuronal and glial Na-K ATPase activities in opposite manner, while it increased neuronal Na-K ATPase, and it decreased the same in glia. An intricate regulation of Na-K ATPase activity in neurons and glia is likely to be responsible for maintenance of ionic homeostasis in the brain during normal situation, which when disturbed including upon REMS loss patho-physiological changes and symptoms are expressed.