Stimulatory role of calcium in rapid eye movement sleep deprivation-induced noradrenaline-mediated increase in Na-K-ATPase activity in rat brain

Neuroscience. 2008 Jul 31;155(1):76-89. doi: 10.1016/j.neuroscience.2008.04.069. Epub 2008 May 6.


Rapid eye movement (REM) sleep deprivation elevates noradrenaline level, which upon acting on alpha1-adrenoceptors increases Na-K-ATPase activity; however, the detailed intracellular mechanism of action was unknown. Since membrane integrity is crucial for maintaining Na-K-ATPase activity as well as ionic exchange and noradrenaline affects membrane lipid-peroxidation, we proposed that the deprivation might modulate membrane lipid-peroxidation, which would modulate intracellular ionic concentration and thereby increase Na-K-ATPase activity. Hence, in this in vivo and in vitro study, rats were deprived of REM sleep for 4 days by the flowerpot method and suitable control experiments were conducted. The deprivation simultaneously decreased membrane lipid-peroxidation as well as increased Na-K-ATPase activity by its dephosphorylation and all the effects were induced by noradrenaline. Further, in vitro experiments showed that hydrogen peroxide (H(2)O(2))-induced enhanced lipid-peroxidation increased synaptosomal calcium (Ca(2+))-influx, which was also prevented by noradrenaline and nifidipine, an L-type Ca(2+)-channel blocker. Additionally, both nifidipine and cyclopiazonic acid, which have opposite effects on intracellular Ca(2+)-concentration, prevented deprivation induced increased Na-K-ATPase activity. We propose that REM sleep deprivation elevates noradrenaline level in the brain that acting on alpha1-adrenoceptor simultaneously reduces membrane lipid-peroxidation but activates phospholipase-C, resulting in closure of L-type Ca(2+)-channel and releasing membrane bound Ca(2+); the latter then dephosphorylates Na-K-ATPase, the active form, causing its increased activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Brain / drug effects*
  • Brain / enzymology
  • Brain / ultrastructure
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Hydrogen Peroxide / pharmacology
  • Lipid Peroxidation / drug effects
  • Lipid Peroxidation / physiology
  • Male
  • Models, Biological
  • Norepinephrine / pharmacology*
  • Oxidants / pharmacology
  • Phosphorylation / drug effects
  • Rats
  • Rats, Wistar
  • Sleep Deprivation / enzymology
  • Sleep Deprivation / pathology*
  • Sleep, REM / physiology*
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism
  • Time Factors


  • Calcium Channel Blockers
  • Oxidants
  • Hydrogen Peroxide
  • Sodium-Potassium-Exchanging ATPase
  • Calcium
  • Norepinephrine