Evidence for chloride ions as intracellular messenger substances in astrocytes.
Cultured rat hippocampal astrocytes were used to investigate the mechanism underlying the suppression of Ba2+-sensitive K+ currents by GABAA receptor activation. Muscimol application had two effects on whole cell currents: opening of the well-known Cl- channel of the GABAA receptor and a secondary longer-lasting blockade of outward K+ currents displaying both peak and plateau phases. This blockade was independent of both Na+ (inside and outside) and ATP in the pipette. It also seemed to be independent of muscimol binding to the receptor because picrotoxin application showed no effect on the K+ conductance. The effect is blocked when anion efflux is prevented by replacing Cl- with gluconate (both inside and out) and is enhanced with more permeant anions such as Br- and I-. Moreover, the effect is reproduced in the absence of muscimol by promoting Cl- efflux via lowering of extracellular Cl- levels. These results, along with the requirement for Cl- efflux in muscimol experiments, show a strong dependency of the secondary blockade on Cl- efflux through the Cl- channel of the GABAA receptor. We therefore conclude that changes in the intracellular Cl- concentration alter the outward K+ conductances of astrocytes. Such a Cl--mediated modulation of an astrocytic K+ conductance will have important consequences for the progression of spreading depression through brain tissue and for astrocytic swelling in pathological situations.
Department of Physiology, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5E5 Canada.
L K
LK
Bekar
W
W
Walz
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D001464:Barium / Q000494:pharmacology; D002478:Cells, Cultured; D018118:Chloride Channels / Q000502:physiology*; D002712:Chlorides / Q000502:physiology*; D005942:Gluconates / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D007700:Kinetics; D009118:Muscimol / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology; D015290:Second Messenger Systems; D012964:Sodium / Q000494:pharmacology / Q000502:physiology
D018118:Chloride Channels; D002712:Chlorides; D005942:Gluconates; D015221:Potassium Channels; D011963:Receptors, GABA-A; D001464:Barium; D009118:Muscimol; D012964:Sodium; C030691:gluconic acid