FUNCTIONALLY DISTINCT CHLORIDE-MEDIATED GABA RESPONSES IN RAT CEREBELLAR GRANULE CELLS CULTURED IN A LOW-POTASSIUM MEDIUM

The patch-clamp technique was used to study whole cell currents evoked by gamma-aminobutyric acid (GABA) in rat cerebellar granule cells cul tured in 5 mM potassium, a condition that favors the development of fu nctional GABAergic synapses. GABA activated both high- and low-sensiti vity receptors. The high-sensitivity receptor had an effective concent ration producing half the maximum response (EC(50)) of 13 mu M, wherea s the low-sensitivity one had an EC(50) of 255 mu M. The GABAA recepto r agonist isoguvacine activated only the high-sensitivity receptor wit h an EC(50) of 16 mu M. When GABA was applied during the desensitized phase of the response elicited by a saturating concentration of isoguv acine, it was still able to induce a small response, whereas when isog uvacine was applied during the desensitizing phase of GABA-evoked curr ent no response was detected. GABA responses were highly heterogeneous regarding their sensitivity to bicuculline. In a small number of cell s (3 of 25), bicuculline (10 mu M) completely abolished GABA-evoked cu rrents. In the majority of the neurons (22 of 25) the blocking effect of bicuculline (100 mu M) was 64 +/- 4% (mean +/- SE). The bicuculline -resistant component was abolished by picrotoxin (100 mu M). In bicucu lline, the dose-response curve for GABA was fitted with a sigmoidal cu rve with an EC(50) value of 209 mu M. These data indicate that functio nal new GABA receptor types with unusual pharmacology could be switche d on by conditions that maintain cells in their undifferentiated state .