Synaptically Released Neurotransmitter Fails to Desensitize Postsynaptic GABAA Receptors in Cerebellar Cultures

Abstract

GABA concentration jump experiments performed on membrane patches predict that postsynaptic GABAAreceptors will become desensitized following the release of the contents of a single GABA-containing synaptic vesicle. To examine this we used a single synaptic bouton stimulation technique to directly examine whether postsynaptic GABAA receptors in cultured cerebellar granule cells exhibit transmitter-induced desensitization. In a large number of recordings, no evidence was found for desensitization of postsynaptic GABAAreceptors by vesicularly released transmitter. This was the case even when as many as 40 vesicles were released from a single bouton within 1.5 s. In addition, postsynaptic depolarization and application of the benzodiazepine flunitrazepam, manipulations previously shown to enhance desensitization of GABAA receptors, failed to unmask transmitter-induced desensitization. In contrast, a single 2- to 3-s application of a high concentration of exogenous GABA was able to depress synaptic responsiveness for up to 70 s. Furthermore, pharmacological depletion of GABA eliminated inhibitory synaptic communication, suggesting that GABA is the transmitter and the desensitization-resistant inhibitory postsynaptic currents are not mediated by a “nondesensitizing” ligand such as β-alanine. Overall our data indicate that a specific desensitization-resistant population of GABAA receptors are present at postsynaptic sites on cultured cerebellar granule cells.