GABA(A) receptor activation triggers a Cl- conductance increase and a K+ channel blockade in cerebellar granule cells.
GABA(A) receptor activation in cerebellar granule cells induced a complex physiological response, namely the activation of a Cl- conductance in concert with a blockade of the resting K+ outward conductance (by 71% as compared to controls). Both responses were mediated by the activation of GABA(A) receptors, since they were both mimicked by the GABA(A) receptor agonist muscimol and antagonized by picrotoxin and bicuculline. A substantial decrease of the mean open time of single, outwardly rectifying K+ channels was triggered by GABA as revealed from cell-attached recordings; this finding implies that an intracellular pathway links GABA(A) receptors and K+ channels. Furthermore, this action of GABA is mediated through the cytoplasm, as experiments with the cell-attached patch-clamp technique show. GABA induced a prominent membrane depolarization ranging from 10 to 25 mV as revealed by current-clamp recordings of gramicidin (or nystatin) permeabilized patches, thus selecting conditions not to perturb the physiological Cl- gradient across the cell. Our findings imply that the GABA-activated Cl- current depolarized the membrane as described for immature neurons. The blockade of the resting K+ channel conductance acts in concert and both mechanisms lead to this substantial depolarizing event.
Labrakakis
C
C
Max-Delbrück-Center for Molecular Medicine, Cellular Neurosciences, Berlin, Germany.
Müller
T
T
Schmidt
K
K
Kettenmann
H
H
D000818:Animals; D001464:Barium / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018118:Chloride Channels / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009118:Muscimol / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D011963:Receptors, GABA-A / Q000502:physiology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001464:Barium; D001640:Bicuculline; D018118:Chloride Channels; D002712:Chlorides; D009118:Muscimol; D010852:Picrotoxin; D026902:Potassium Channel Blockers; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid