GABA(A) RECEPTOR ACTIVATION TRIGGERS A CL- CONDUCTANCE INCREASE AND AK+ CHANNEL BLOCKADE IN CEREBELLAR GRANULE CELLS

GABA(A) receptor activation in cerebellar granule cells induced a comp lex 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 acti vation of GABA(A) receptors, since they were both mimicked by the GABA (A) receptor agonist muscimol and antagonized by picrotoxin and bicucu lline. A substantial decrease of the mean open time of single, outward ly rectifying K+ channels was triggered by GABA as revealed from cell- attached recordings; this finding implies that an intracellular pathwa y 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 sel ecting conditions not to perturb the physiological Cl- gradient across the cell. Our findings imply that the GABA-activated Cl- current depo larized the membrane as described for immature neurons. The blockade o f the resting K+ channel conductance acts in concert and both mechanis ms lead to this substantial depolarizing event. (C) 1997 IBRO.