title: Requirement of glycogenolysis for uptake of increased extracellular K+ in astrocytes: potential implications for K+ homeostasis and glycogen usage in brain.
abstract: The importance of astrocytic K(+) uptake for extracellular K(+) ([K(+)](e)) clearance during neuronal stimulation or pathophysiological conditions is increasingly acknowledged. It occurs by preferential stimulation of the astrocytic Na(+),K(+)-ATPase, which has higher K(m) and V(max) values than its neuronal counterpart, at more highly increased [K(+)](e) with additional support of the cotransporter NKCC1. Triggered by a recent DiNuzzo et al. paper, we used administration of the glycogenolysis inhibitor DAB to primary cultures of mouse astrocytes to determine whether K(+) uptake required K(+)-stimulated glycogenolysis. KCl was increased by either 5 mM (stimulating only the Na(+),K(+)-ATPase) or 10 mM (stimulating both transporters) in glucose-containing saline media prepared to become iso-osmotic after the addition. DAB completely inhibited both uptakes, the Na(+),K(+)-ATPase-mediated by preventing Na(+) uptake for stimulation of its intracellular Na(+)-activated site, and the NKCC1-mediated uptake by inhibition of depolarization- and L-channel-mediated Ca(2+) uptake. Drugs inhibiting the signaling pathways involved in either of these processes also abolished K(+) uptake. Assuming similar in vivo characteristics, partly supported by literature data, K(+)-stimulated astrocytic K(+) uptake must discontinue after normalization of extracellular K(+). This will allow Kir1.4-mediated release and reuptake by the less powerful neuronal Na(+),K(+)-ATPase.
authors.affiliation: Department of Clinical Pharmacology, China Medical University, No. 92 Beier Road, Heping District, Shenyang, People's Republic of China.
authors.forename: Junnan
authors.initials: J
authors.lastname: Xu
authors.forename: Dan
authors.initials: D
authors.lastname: Song
authors.forename: Zhanxia
authors.initials: Z
authors.lastname: Xue
authors.forename: Li
authors.initials: L
authors.lastname: Gu
authors.forename: Leif
authors.initials: L
authors.lastname: Hertz
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
mesh_terms: D000818:Animals; D001089:Arabinose / Q000494:pharmacology; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D006003:Glycogen / Q000378:metabolism; D050261:Glycogenolysis / Q000187:drug effects; D006706:Homeostasis / Q000502:physiology*; D050113:Imino Furanoses / Q000494:pharmacology; D047028:Macrocyclic Compounds / Q000494:pharmacology; D051379:Mice; D008985:Monensin / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D028021:Sodium-Potassium-Chloride Symporters / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2; D013402:Sugar Alcohols / Q000494:pharmacology
chemical_list: D050113:Imino Furanoses; D047028:Macrocyclic Compounds; D010080:Oxazoles; C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D013402:Sugar Alcohols; C511704:xestospongin C; C058137:1,4-dideoxy-1,4-iminoarabinitol; D006003:Glycogen; D008985:Monensin; D001089:Arabinose; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium