Rapid Eye Movement Sleep Deprivation Associated Increase in Na-K ATPase Activity in the Rat Brain is Due to Noradrenaline Induced α1-Adrenoceptor Mediated Increased α-Subunit of the Enzyme

Neurochem Res. 2015 Aug;40(8):1747-57. doi: 10.1007/s11064-015-1660-8. Epub 2015 Jul 7.

Abstract

Rapid eye movement sleep (REMS) modulates Na-K ATPase activity and maintains brain excitability. REMS deprivation (REMSD)-associated increased Na-K ATPase activity is mediated by noradrenaline (NA) acting on α1-adrenoceptor (AR) in the brain. It was shown that NA-induced increased Na-K ATPase activity was due to allosteric modulation as well as increased turnover of the enzyme. Although the former has been studied in detail, our understanding on the latter was lacking, which we have studied. Male Wistar rats were REMS deprived for 4-days by classical flower-pot method; suitable control experiments were conducted. In another set, α1-AR antagonist prazosin (PRZ) was i.p. injected 48 h REMSD onward. At the end of experiments rats were sacrificed by cervical dislocation and brains were removed. Synaptosomes prepared from the brains were used to estimate Na-K ATPase activity as well as protein expressions of different isoforms of the enzyme subunits using western blot. REMSD significantly increased synaptosomal Na-K ATPase activity and that was due to differential increase in the expressions of α1-, α2- and α3-isoforms, but not that of β1- and β2-isoforms. PRZ reduced the REMSD-induced increased Na-K ATPase activity and protein expressions. We also observed that the increased Na-K ATPase subunit expression was not due to enhanced mRNA synthesis, which suggests the possibility of post-transcriptional regulation. Thus, the findings suggest that REMSD-associated increased Na-K ATPase activity is due to elevated level of α-subunit of the enzyme and that is induced by NA acting on α1-AR mediated mRNA-stabilization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists / pharmacology
  • Animals
  • Brain / drug effects
  • Brain / enzymology*
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Male
  • Norepinephrine / pharmacology*
  • Norepinephrine / physiology
  • Protein Subunits / biosynthesis*
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-1 / biosynthesis*
  • Sleep Deprivation / enzymology*
  • Sleep, REM / drug effects
  • Sleep, REM / physiology*
  • Sodium-Potassium-Exchanging ATPase / metabolism*

Substances

  • Adrenergic alpha-1 Receptor Antagonists
  • Protein Subunits
  • Receptors, Adrenergic, alpha-1
  • Sodium-Potassium-Exchanging ATPase
  • Norepinephrine