Noradrenaline acting on alpha1-adrenoceptor mediates REM sleep deprivation-induced increased membrane potential in rat brain synaptosomes.
We hypothesized that one of the functions of REM sleep is to maintain brain excitability and therefore, REM sleep deprivation is likely to modulate neuronal transmembrane potential; however, so far there was no direct evidence to support the claim. In this study a cationic dye, 3,3'-diethylthiacarbocyanine iodide was used to estimate the potential in synaptosomal samples prepared from control and REM sleep deprived rat brains. The activity of Na-K-ATPase that maintains the transmembrane potential was also estimated in the same sample. Further, the roles of noradrenaline and alpha1-adrenoceptor in mediating the responses were studied both in vivo as well as in vitro. Rats were REM sleep deprived for 4 days by the classical flower-pot method; large platform and recovery controls were carried out in addition to free-moving control. The fluorescence intensity increased in samples prepared from REM sleep deprived rat brain as compared to control, which reflected synaptosomal depolarization after deprivation. The Na-K-ATPase activity also increased in the same deprived sample. Furthermore, both the effects were mediated by noradrenaline acting on alpha1-adrenoceptors in the brain. This is the first direct evidence showing that REM sleep deprivation indeed increased neuronal depolarization, which is the likely cause for increased brain excitability, thus supporting our hypothesis and the effect was mediated by noradrenaline acting through the alpha1-adrenoceptor.
Das
Gitanjali
G
School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Mallick
Birendra Nath
BN
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins; D009638:Norepinephrine / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D012892:Sleep Deprivation / Q000503:physiopathology*; D012895:Sleep, REM / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013574:Synaptosomes / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; C448722:DISC2 gene product, human; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D000254:Sodium-Potassium-Exchanging ATPase; D009638:Norepinephrine; D011224:Prazosin