Chloride Channel Modulation at GABAergic Synapses in Primary Cultures of Cortical Neurons
The opening of Cl− channels mediated by γ-aminobutyric acid (GABA) can be modulated by benzodiazepine (BZ) or beta-carboline (BC) recognition site ligands (Choi et al., 1977) which per se do not act on C1− channels. We studied these ligands at GABAergic synapses in primary cultures of rat cortical neurons and selected for this study flunitrazepam (a positive allosteric modulator) DMCM* (a negative allosteric modulator) and the imidazobenzodiazepine RO-151788** (a high affinity ligand with low intrinsic activity) (Hunkeler et al., 1981). Chan et al. (1985) have shown that flunitrazepam facilitates the Cl− fluxes elicited by exogenous GABA in primary cultures of CNS neurons and DMCM decreases these ionic fluxes; moreover RO-151788 blocks the action of both compounds showing little or no intrinsic action. In the present study, the modulation of GABA mediated Cl− channel opening was studied during the release of GABA from presynaptic endings at GABAergic synapses formed among rat cortical neurons in primary culture. The direct action of these three compounds on Cl− channel was also studied in membrane patches excised from these neurons. This study was intended to further understanding of the physiological role of the allosteric modulation of GABA recognition sites by exogenous and endogenous ligands of BZ-BC recognition sites.
KeywordsSynaptic Current Membrane Patch Decay Time Constant GABAergic Synapse Positive Allosteric Modulator
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