Kinetic analysis of evoked IPSCs discloses mechanism of antagonism of synaptic GABAA receptors by picrotoxin.

British Journal of Pharmacology
A R KorshoejJ D C Lambert

Abstract

Although picrotoxin is a well-established antagonist of GABA(A) receptors, detailed studies of its action on inhibitory synaptic transmission have not previously been made. Electrophysiological techniques were used to study the action of picrotoxin on inhibitory postsynaptic currents (IPSCs) evoked in hippocampal neurones, in culture and slice preparations prepared from Wistar rat embryos and juveniles, respectively. Picrotoxin gradually reduced the amplitude of GABA(A) receptor-mediated eIPSCs in a concentration-dependent manner. This was accompanied by a marked acceleration of the eIPSC decay kinetics, which, in contrast to the effect on amplitude, developed immediately and was completely reversed on washing. The decaying phase of the IPSC could be resolved into two components; 30 microM picrotoxin reduced tau(fast) by 34% and increased its relative amplitude, while tau(slow) was reduced by 38%, and its relative amplitude decreased. The area under the decaying phase of the normalized eIPSC showed an immediate reduction by 36% in 30 microM picrotoxin. With increasing concentrations of picrotoxin, this normalized area converged towards 55% of the control, indicating that the rate of relaxation and block has a finite maximum. Th...Continue Reading

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Citations

Sep 14, 2013·Chemical Research in Toxicology·Timothy S CarpenterFelice C Lightstone
Jan 21, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hongdian YangDietmar Plenz
Jul 26, 2012·Neuropharmacology·Shelley H HuangRujee K Duke
May 27, 2014·Frontiers in Cellular Neuroscience·Rasmus K ChristensenJean-François Perrier
Sep 4, 2014·PloS One·Valentina CartaErwin Sigel

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