Functionally distinct chloride-mediated GABA responses in rat cerebellar granule cells cultured in a low potassium medium. Martina, Marco, Caterina Virginio and Enrico Cherubini. Biophysics Sector, International School for Advanced Studies (SISSA), Via Beirut 2-4, 34014 Trieste, Italy.
APStracts 3:0231N, 1996.
The patch clamp technique was used to study whole cell currents evoked by (- aminobutyric acid (GABA) in rat cerebellar granule cells cultured in 5 mM potassium, a condition that favours the development of functional GABAergic synapses. GABA activated both high and low sensitivity receptors. The high sensitivity receptor had an EC50 of 13 (M whereas the low sensitivity one had an EC50 of 255 (M. The GABAA receptor agonist isoguvacine activated only the high sensitivity receptor with an EC50 of 16 (M. When GABA was applied during the desensitized phase of the response elicited by a saturating concentration of isoguvacine, it was still able to induce a small response whereas when isoguvacine was applied during the desensitizing phase of GABA-evoked current no response was detected. GABA responses were highly heterogeneous regarding their sensitivity to bicuculline. In a small number of cells (3/25), bicuculline (10 (M) completely abolished GABA-evoked currents. In the majority of the neurons (22/25) the blocking effect of bicuculline (100 (M) was 64 ( 4 %.The bicuculline-resistant component was abolished by picrotoxin (100 (M). In bicuculline, the dose/response curve for GABA was fitted with a sigmoidal curve with an EC50 value of 209 (M. These data indicate that functional new GABA receptor types with unusual pharmacology could be swithched on by conditions that maintain cells in their undifferentiated state.

Received 19 June 1996; accepted in final form 30 September 1996.
APS Manuscript Number J491-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996