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Astrocytic glycogenolysis: mechanisms and functions

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Abstract

Until the demonstration little more than 20 years ago that glycogenolysis occurs during normal whisker stimulation glycogenolysis was regarded as a relatively uninteresting emergency procedure. Since then, a series of important astrocytic functions has been shown to be critically dependent on glycogenolytic activity to support the signaling mechanisms necessary for these functions to operate. This applies to glutamate formation and uptake and to release of ATP as a transmitter, stimulated by other transmitters or elevated K+ concentrations and affecting not only other astrocytes but also most other brain cells. It is also relevant for astrocytic K+ uptake both during the period when the extracellular K+ concentration is still elevated after neuronal excitation, and capable of stimulating glycogenolytic activity, and during the subsequent undershoot after intense neuronal activity, when glycogenolysis may be stimulated by noradrenaline. Both elevated K+ concentrations and several transmitters, including the β-adrenergic agonist isoproterenol and vasopressin increase free cytosolic Ca2+ concentration in astrocytes, which stimulates phosphorylase kinase so that it activates the transformation of the inactive glycogen phosphorylase a to the active phosphorylase b. Contrary to common belief cyclic AMP plays at most a facilitatory role, and only when free cytosolic Ca2+ concentration is also increased. Cyclic AMP is not increased during activation of glycogenolysis by either elevated K+ concentrations or the stimulation of the serotonergic 5-HT2B receptor. Not all agents that stimulate glycogenolysis do so by directly activating phophorylase kinase—some do so by activating processes requiring glycogenolysis, e.g. for synthesis of glutamate.

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  1. Department of Clinical Pharmacology, China Medical University, No. 92 Beier Road, Heping District, 110001, Shenyang, Peoples’ Republic of China

    Leif Hertz, Junnan Xu, Dan Song, Ting Du, Baoman Li, Enzhi Yan & Liang Peng

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  1. Leif Hertz
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  2. Junnan Xu
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  3. Dan Song
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  4. Ting Du
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  5. Baoman Li
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  6. Enzhi Yan
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  7. Liang Peng
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Correspondence to Liang Peng.

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Hertz, L., Xu, J., Song, D. et al. Astrocytic glycogenolysis: mechanisms and functions. Metab Brain Dis 30, 317–333 (2015). https://doi.org/10.1007/s11011-014-9536-1

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  • DOI: https://doi.org/10.1007/s11011-014-9536-1

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