Ionic mechanisms in glutamate-induced astrocyte swelling: role of K+ influx.
L-Glutamate (L-GLU) induced astrocyte swelling in a time- and concentration-dependent, as well as Na+- and Ca2+-dependent, and Cl(-)-independent manner. Swelling was prevented by MK-801, cystine, and ouabain. Since L-GLU swelling is ionically dependent, we determined the role of various ions in such swelling. Our results indicate that K+ uptake plays a major role in the mechanism of L-GLU-induced astrocyte swelling. Like swelling, K+ uptake is dependent on Ca2+ and Na+, but not on Cl-. Likewise, K+ uptake was inhibited by MK-801, cystine, and ouabain. The K+ channel blockers, Ba2+ and tetraethylammonium, partially prevented L-GLU-induced swelling. In addition to K+ channels, K+ influx may also be mediated through Na+/K+-ATPase, as its activity is increased by L-GLU uptake along with the required Na+. Taken together, the data suggest that K+ influx plays a key role in the mechanism of L-GLU-mediated astrocyte swelling.
Bender
A S
AS
Veterans Affairs Medical Center, Department of Pathology, University of Miami School of Medicine, Florida 33101, USA.
Schousboe
A
A
Reichelt
W
W
Norenberg
M D
MD
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D017136:Ion Transport; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors
D002712:Chlorides; D018690:Excitatory Amino Acid Agonists; D014179:Neurotransmitter Uptake Inhibitors; D026902:Potassium Channel Blockers; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D002118:Calcium