title: Noradrenergic β-Adrenoceptor-Mediated Intracellular Molecular Mechanism of Na-K ATPase Subunit Expression in C6 Cells.
abstract: Rapid eye movement sleep deprivation-associated elevated noradrenaline increases and decreases neuronal and glial Na-K ATPase activity, respectively. In this study, using C6 cell-line as a model, we investigated the possible intracellular molecular mechanism of noradrenaline-induced decreased glial Na-K ATPase activity. The cells were treated with noradrenaline in the presence or absence of adrenoceptor antagonists, modulators of extra- and intracellular Ca++and modulators of intracellular signalling pathways. We observed that noradrenaline acting on β-adrenoceptor decreased Na-K ATPase activity and mRNA expression of the catalytic α2-Na-K ATPase subunit in the C6 cells. Further, cAMP and protein kinase-A mediated release of intracellular Ca++played a critical role in such decreased α2-Na-K ATPase expression. In contrast, noradrenaline acting on β-adrenoceptor up-regulated the expression of regulatory β2-Na-K ATPase subunit, which although was cAMP and Ca++dependent, was independent of protein kinase-A and protein kinase-C. Combining these with previous findings (including ours) we have proposed a working model for noradrenaline-induced suppression of glial Na-K ATPase activity and alteration in its subunit expression. The findings help understanding noradrenaline-associated maintenance of brain excitability during health and altered states, particularly in relation to rapid eye movement sleep and its deprivation when the noradrenaline level is naturally altered.
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
authors.forename: Megha
authors.initials: M
authors.lastname: Amar
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Singh
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India. remsbnm@yahoo.com.
authors.forename: Birendra Nath
authors.initials: BN
authors.lastname: Mallick
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D007424:Intracellular Fluid / Q000187:drug effects / Q000201:enzymology*; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012964:Sodium / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D002227:Carbazoles; D004791:Enzyme Inhibitors; D021122:Protein Subunits; D011758:Pyrroles; D011943:Receptors, Adrenergic, beta; C057416:KT 5720; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Brain excitability; Ca++; PKA; Propranolol; REM sleep; cAMP