Does Endogenous Norepinephrine Regulate Potassium Homeostasis and Metabolism in Rat Cerebral Cortex?

Sick, Thomas J.; Hertz, Leif; LaManna, Joseph C.; Rosenthal, Myron; Flaggman, Allan; Harik, Sami I.

doi:10.1038/jcbfm.1982.36

Cited by 6 publications

(4 citation statements)

References 18 publications

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“…Despite this marked depletion of norepinephrine, neither the maximal capacity nor the affinity of specific ouabain binding to crude membranes of the cerebral cortex was significantly altered by the lesion (Table 1). These findings are consistent with previous results from this laboratory, which showed that LC lesion, and the resultant norepinephrine depletion of the cerebral cortex, was not associated with a significant decrease in Na+/K+-ATPase activity of cortical membrane preparations when assayed in vitro (19). More important, norepinephrine depletion had no effect on extracellular K+ concentrations in the rat cerebral cortex at rest, nor did it affect the kinetics of (20,21), who observed only a modest decrease (about 15%) in Na+/K+-ATPase activity and specific ouabain binding after cerebral norepinephrine depletion.…”

Section: Resultssupporting

confidence: 83%

“…The reaction mixture (0.25 ml) contained 2 mM TrisATP (vanadium-free grade), 100 mM NaCl, 2 mM MgCl2, 10 mM Tris buffer (pH 7.4), and [3H]ouabain (19)(20)(21) Ci/mmol, New England Nuclear; 1 Ci = 37 GBq) in concentrations that ranged from 5 to 500 nM. The amount of tissue protein ranged from 20 to 50 ,g for cortical membranes and from 50 to 100 ,g for cerebral microvessels.…”

Section: Methodsmentioning

confidence: 99%

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Blood--brain barrier sodium/potassium pump: modulation by central noradrenergic innervation.

Harik¹

1986

Proc. Natl. Acad. Sci. U.S.A.

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The active transport of Na+ and K+ across the blood-brain barrier by the membrane-bound enzyme Na+/K+-activated ATPase of brain microvessel endothelial cells has a major role in the maintenance of brain water and electrolyte homeostasis. To test whether the putative noradrenergic innervation of cerebral microvessels from the nucleus locus ceruleus contributes to the regulation of Na+/K+-ATPase activity of the blood-brain barrier, specific [3H]ouabainbinding studies were performed on cerebral microvessels and crude cortical membranes obtained from Wistar rats with unilateral 6-hydroxydopamine lesion of the nucleus locus ceruleus. Such lesion depleted norepinephrine by about 90% in the ipsilateral cerebral cortex without affecting the contralateral cortex.[3lH]Ouabain binding to membranes of cerebral cortex and the cerebral microvessels was specific and saturable. The maximal ouabain-binding capacity in microvessels of the ipsilateral, norepinephrine-depleted, cerebral cortex was reduced by about 40%, without change in the affinity of binding.[3H]Ouabain binding to crude membrane fractions of the cerebral cortex was not significantly affected by locus ceruleus lesion. The results suggest that Na+/K+-ATPase activity of cerebral microvessels, and the consequent transport of Na+ and K+ across the blood-brain barrier, is modulated by noradrenergic innervation from the locus ceruleus.

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Section: Resultssupporting

confidence: 83%

Section: Methodsmentioning

confidence: 99%

Blood--brain barrier sodium/potassium pump: modulation by central noradrenergic innervation.

Harik¹

1986

Proc. Natl. Acad. Sci. U.S.A.

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“…Participation of adrenergic stimulation in cellular K + uptake, specifically at small but not at larger increases in [K + ] o after stimulation in vivo, was also suggested by Sick et al (). These authors studied kinetics of the return of [K + ] o to control levels in anesthetized rats with unilateral destruction of locus coeruleus, the origin of noradrenergic fibers to the brain, at different stimulated values of [K + ] o (resulting from different stimulation intensity).…”

Section: The Astrocytic Na+k+‐atpase Is Also Stimulated By Isoprotersupporting

confidence: 54%

Roles of astrocytic Na⁺,K⁺‐ATPase and glycogenolysis for K⁺ homeostasis in mammalian brain

Hertz

Gerkau

et al. 2014

J of Neuroscience Research

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Neuronal excitation increases extracellular K+ concentration ([K+]o) in vivo and in incubated brain tissue by stimulation of postsynaptic glutamatergic receptors and by channel‐mediated K+ release during action potentials. Convincing evidence exists that subsequent cellular K+ reuptake occurs by active transport, normally mediated by Na+,K+‐ATPase. This enzyme is expressed both in neurons and in astrocytes but is stimulated by elevated [K+]o only in astrocytes. This might lead to an initial K+ uptake in astrocytes, followed by Kir4.1‐mediated release and neuronal reuptake. In cell culture experiments, K+‐stimulated glycogenolysis is essential for operation of the astrocytic Na+,K+‐ATPase resulting from the requirement for glycogenolysis in a pathway leading to uptake of Na+ for costimulation of its intracellular sodium‐binding site. The astrocytic but not the neuronal Na+,K+‐ATPase is additionally stimulated by isoproterenol, a β‐adrenergic agonist, but only at nonelevated [K+]o. This effect is also glycogenolysis dependent and might play a role during poststimulatory undershoots. Attempts to replicate dependence on glycogenolysis for K+ reuptake in glutamate‐stimulated brain slices showed similar [K+]o recovery half‐lives in the absence and presence of the glycogenolysis inhibitor 1,4‐dideoxy‐1,4‐imino‐d‐arabinitol. The undershoot was decreased, but to the same extent as an unexpected reduction of peak [K+]o increase. A potential explanation for this difference from the cell culture experiments is that astrocytic glutamate uptake might supply the cells with sufficient Na+. Inhibition of action potential generation by tetrodotoxin caused only a marginal, nonsignificant decrease in stimulated [K+]o in brain slices, hindering the evaluation if K+ reaccumulation after action potential propagation requires glycogenolysis in this preparation. © 2014 W iley Periodicals, Inc.

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“…That the clearance of extracellular potassium, elevated by cortical stimulation, is slowed by barbitu rate administration supports the former ex planation as the cause of slow cytochrome a.aj re-reduction with that drug [20]. On the other hand, cerebral NE depletion in Wistar rats does not alter the rate of extracellular potassium clearance after electrocortical stimulation [40,41], There is now evidence that the availability of substrates to re-reduce cytochrome a.aj after increased cortical ac tivity may be decreased when cortical NE is depleted because of decreased glycogenolysis [11], There is also ample evidence in the lit erature to suggest decreased substrate mobili zation in the cerebral cortex of aged rats. This is based on decreased phosphofructokinase activity, the rate-limiting enzyme in glycoly sis [24], and decreased NAD isocitrate dehy drogenase activity [29,47], an important en zyme in the Krebs cycle.…”

Section: Discussionmentioning

confidence: 99%

Abnormalities of Cerebral Oxidative Metabolism with Aging and Their Relation to the Central Noradrenergic System

et al. 1983

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Cerebral oxidative metabolism was studied in vivo by monitoring redox shifts of cytochrome c oxidase in response to direct electrical stimulation of the cerebral cortex in Fischer-344 rats at 3 and 28 months of age. Such activation results in a transient oxidation of cytochrome oxidase associated with brief increase in local cerebral blood volume. In aged rats, the rates of the transient redox responses of cytochrome oxidase (i.e. initial oxidation followed by re-reduction) are slowed by about 50% in comparison to young rats. Cortical norepinephrine was similar in both age-groups. However, while depletion of cortical norepinephrine causes slowing of the rate of re-reduction in young rats by about 50%, such depletion had no effect on the already slow kinetics of the redox shifts of aged rats. Vascular reactivity to increased metabolic demands, defined by the amplitude ratio of the blood volume increase to the cytochrome oxidation, is increased with age but attenuated by norepinephrine depletion in both age-groups. These results suggest that: (1) cerebral cortical levels of norepinephrine do not decline with age in the Fischer-344 rat; (2) development of an age-related impairment in the capability of cerebral oxidative metabolism to respond to conditions of heightened metabolic demands; (3) such impairment is not worsened by depletion of cerebral norepinephrine; (4) exaggerated vascular reactivity to increased metabolic requirement in aging indicates decreased provision of oxygen and metabolic substrates, and (5) this vascular reactivity is mediated by central noradrenergic mechanisms.

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Does Endogenous Norepinephrine Regulate Potassium Homeostasis and Metabolism in Rat Cerebral Cortex?

Cited by 6 publications

References 18 publications

Blood--brain barrier sodium/potassium pump: modulation by central noradrenergic innervation.

Blood--brain barrier sodium/potassium pump: modulation by central noradrenergic innervation.

Roles of astrocytic Na⁺,K⁺‐ATPase and glycogenolysis for K⁺ homeostasis in mammalian brain

Abnormalities of Cerebral Oxidative Metabolism with Aging and Their Relation to the Central Noradrenergic System

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Does Endogenous Norepinephrine Regulate Potassium Homeostasis and Metabolism in Rat Cerebral Cortex?

Cited by 6 publications

References 18 publications

Blood--brain barrier sodium/potassium pump: modulation by central noradrenergic innervation.

Blood--brain barrier sodium/potassium pump: modulation by central noradrenergic innervation.

Roles of astrocytic Na+,K+‐ATPase and glycogenolysis for K+ homeostasis in mammalian brain

Abnormalities of Cerebral Oxidative Metabolism with Aging and Their Relation to the Central Noradrenergic System

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Roles of astrocytic Na⁺,K⁺‐ATPase and glycogenolysis for K⁺ homeostasis in mammalian brain