Relative picrotoxin insensitivity distinguishes ionotropic GABA receptor-mediated IPSCs in hippocampal interneurons.
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 CA1 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(A) 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.
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects*; D007478:Iontophoresis; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D018079:Receptors, GABA / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects; D000077334:Zolpidem; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology
D001640:Bicuculline; D018755:GABA Agonists; D018756:GABA Antagonists; D018757:GABA Modulators; D010424:Pentobarbital; D010852:Picrotoxin; D011725:Pyridines; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D000077334:Zolpidem; D005680:gamma-Aminobutyric Acid; C087200:GABA-C receptor