title: Roles of astrocytic Na(+),K(+)-ATPase and glycogenolysis for K(+) homeostasis in mammalian brain.
abstract: 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.
authors.affiliation: Laboratory of Brain Metabolic Diseases, Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, People's Republic of China.
authors.forename: Leif
authors.initials: L
authors.lastname: Hertz
authors.affiliation: Institute of Neurobiology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Niklas J
authors.initials: NJ
authors.lastname: Gerkau
authors.affiliation: Laboratory of Brain Metabolic Diseases, Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, People's Republic of China.
authors.forename: Junnan
authors.initials: J
authors.lastname: Xu
authors.affiliation: Institute of Neurobiology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Durry
authors.affiliation: Laboratory of Brain Metabolic Diseases, Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Song
authors.affiliation: Institute of Neurobiology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Christine R
authors.initials: CR
authors.lastname: Rose
authors.affiliation: Laboratory of Brain Metabolic Diseases, Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000166:cytology*; D050261:Glycogenolysis / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D011188:Potassium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium
keywords: K+; Na+,K+-ATPase; astrocytes; brain slice; glycogenolysis