title: KCl movements during potassium-induced cytotoxic swelling of cultured astrocytes.
abstract: Astrocytes in primary cultures from mouse cortex were used to investigate the ionic mechanism of cytotoxic swelling which develops after exposure of the cells to 60 mM K+ under isosmotic conditions. Radiotracer analysis combined with a washing efflux method were used to analyze ion changes. We found that both the K+ and the Cl- content increased by about 100% within 1 min after increasing the external K+, and remained constant for 30 min thereafter. The mechanisms, i.e., Na+,K+-ATPase-mediated transport and NaCl/KCl contransport, that are involved in glial ion homeostasis in physiologic situations (extracellular K+ increase to 12 mM) are disturbed in this system and do not contribute to the cytotoxic swelling induced by pathologic K+ concentrations. The Na+,K+-ATPase-mediated K+ uptake is not additionally stimulated by the pathologic K+ increase. The NaCl/KCl cotransport was minimal, presumably due to a severe reduction of the Na+ driving force by the depolarization. The mechanisms of this pathological swelling were found to consist mainly of a passive KCl influx. This influx is mediated by a disturbance of the Donnan equilibrium. It probably involves an increase of the Cl- permeability by activation of a previously described voltage-dependent Cl- channel, which is closed under physiological conditions. However, it was found that the intracellular Cl- accumulation did not completely match the corresponding K+ accumulation. Possible reasons for this anion deficit are discussed.
authors.affiliation: Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
authors.forename: W
authors.initials: W
authors.lastname: Walz
authors.forename: S
authors.initials: S
authors.lastname: Mukerji
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001464:Barium / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D002712:Chlorides / Q000378:metabolism; D005665:Furosemide / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology*; D011189:Potassium Chloride / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D002712:Chlorides; D001464:Barium; D010042:Ouabain; D011189:Potassium Chloride; D005665:Furosemide; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium