Stimulatory role of calcium in rapid eye movement sleep deprivation-induced noradrenaline-mediated increase in Na-K-ATPase activity in rat brain.
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.
Das
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G
School of Life Sciences, Jawaharlal Nehru University, Baba Gang Nath Marg, New Delhi, India.
Gopalakrishnan
A
A
Faisal
M
M
Mallick
B N
BN
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008954:Models, Biological; D009638:Norepinephrine / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012892:Sleep Deprivation / Q000201:enzymology / Q000473:pathology*; D012895:Sleep, REM / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D002121:Calcium Channel Blockers; D016877:Oxidants; D006861:Hydrogen Peroxide; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium; D009638:Norepinephrine