Journal
NEUROPHARMACOLOGY
Volume 43, Issue 4, Pages 726-736Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0028-3908(02)00123-5
Keywords
inhibition; GABA(A) receptors; CA1; guinea pig; iontophoresis
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Inhibitory GABAergic signalling in the hippocampus plays an important role in synchronizing principal cells and regulating the excitability of this seizure-prone structure. Distinct mechanisms modulate release from GABAergic terminals in the hippocampus, depending on whether the postsynaptic partner is an interneuron or a principal cell. Here, we report that postsynaptic ionotropic GABA receptors in principal cells and interneurons also show a striking pharmacological difference. The broad-spectrum antagonist picrotoxin (PTX) was less potent at blocking IPSCs evoked in stratum radiatum interneurons than in pyramidal neurons in the CAI region. GABA-evoked currents in membrane patches from interneurons showed a smaller mean unitary conductance than in patches from pyramidal neurons. Because retinal GABA(C) receptors show decreased picrotoxin sensitivity and conductance, we examined the effect of the GABA(C) receptor agonist cis-aminocrotonic acid (CACA). Although this agent evoked picrotoxin-resistant currents in interneurons, these were enhanced by the GABA, allosteric modulator pentobarbital. Moreover, both picrotoxin-resistant IPSCs and CACA-evoked currents were blocked by the GABA(A) receptor-selective antagonist bicuculline. The presence of relatively picrotoxin-resistant GABA(A) receptors in interneurons provides a potential target for agents to modulate the activity of sub-populations of hippocampal neurons. (C) 2002 Elsevier Science Ltd. All rights reserved.
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