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.
Bekar
L K
LK
Department of Physiology, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5E5 Canada.
Walz
W
W
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