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Neuroactive steroids induce GABA(A) receptor-mediated depolarizing postsynaptic potentials in hippocampal CA1 pyramidal cells of the rat

Item Type:Article
Title:Neuroactive steroids induce GABA(A) receptor-mediated depolarizing postsynaptic potentials in hippocampal CA1 pyramidal cells of the rat
Creators Name:Burg, M. and Heinemann, U. and Schmitz, D.
Abstract:Intracellular recordings were performed in area CA1 pyramidal cells of rat hippocampal slices to determine the effects of certain steroids on inhibitory postsynaptic potentials/currents (IPSP/Cs) mediated by GABA(A) receptors. Following application of the steroids 5{alpha}-pregnan-3{alpha},21-diol-20-one (5{alpha}-THDOC), {alpha}xalone and 5beta-pregnan-3{alpha}-ol-20-one (pregnanolone) hyperpolarizing PSPs developed into biphasic responses consisting of an early hyperpolarizing and a late depolarizing PSP sequence. Steroid-induced depolarizing PSPs could be elicited in the presence of antagonists to non-NMDA, NMDA, and GABA(B) receptors, indicating that these receptor types do not contribute significantly to the initiation of these responses. Depolarizing PSPs were completely blocked by both GABA(A) receptor antagonists bicuculline and t-butylbicyclophosphorothionat (TBPS) providing evidence for their mediation by GABA(A) receptors. The reversal potential of steroid-induced late inward PSCs, measured in single-electrode voltage clamp, was -29.9+/-5.3 mV, whereas the early outward current, which corresponded to the early hyperpolarizing component of PSPs, reversed at -68.2+/-1.5 mV. Depolarizing PSPs and late inward PSCs were sensitive to reduction of extracellular [HCO3-] and block of carbonic anhydrase by application of acetazolamide. The results suggest that certain neuroactive steroids can induce GABA(A) receptor-mediated depolarizing PSPs, which are dependent on HCO3-.
Keywords:Bicarbonate, Pregnane Steroids, Single-Electrode Voltage Clamp, TBPS, Animals, Rats
Source:European Journal of Neuroscience
ISSN:0953-816X
Publisher:Blackwell Publishing (U.K.)
Volume:10
Number:9
Page Range:2880-2886
Date:September 1998
Official Publication:https://doi.org/10.1111/j.1460-9568.1998.00297.x
PubMed:View item in PubMed

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