Comparison of Steroid Modulation of Spontaneous Inhibitory Postsynaptic Currents in Cultured Hippocampal Neurons and Steady-State Single-Channel Currents from Heterologously Expressed α1β2γ2L GABA(A) Receptors

Molecular Pharmacology
Sampurna ChakrabartiGustav Akk

Abstract

Neuroactive steroids are efficacious modulators of γ-aminobutyric acid type A receptor (GABA(A)) receptor function. The effects of steroids on the GABA(A) receptor are typically determined by comparing steady-state single-channel open probability or macroscopic peak responses elicited by GABA in the absence and presence of a steroid. Due to differences in activation conditions (exposure duration, concentration of agonist), it is not obvious whether modulation measured using typical experimental protocols can be used to accurately predict the effect of a modulator on native receptors under physiologic conditions. In the present study, we examined the effects of 14 neuroactive steroids and analogs on the properties of spontaneous inhibitory postsynaptic currents (sIPSCs) in cultured rat hippocampal neurons. The goal was to determine whether the magnitude of modulation of the decay time course of sIPSCs correlates with the extent of modulation and kinetic properties of potentiation as determined in previous single-channel studies. The steroids were selected to cover a wide range of efficacy on heterologously expressed rat α1β2γ2L GABA(A) receptors, ranging from essentially inert to highly efficacious (strong potentiators of single...Continue Reading

References

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Dec 18, 2001·The Journal of Physiology·J H Steinbach, G Akk
Apr 23, 2004·Molecular Pharmacology·Steven MennerickCharles F Zorumski
May 18, 2004·The Journal of Physiology·Gustav AkkJoe Henry Steinbach
Dec 16, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Gustav AkkSteven Mennerick
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Feb 4, 2006·The Journal of Physiology·Gareth M C Lema, Anthony Auerbach
Apr 22, 2008·Nature Reviews. Neuroscience·Nicholas P Franks
Sep 3, 2010·Current Neuropharmacology·Gustav AkkJoe Henry Steinbach
Dec 2, 2010·European Journal of Pharmacology·Hye-Mi ParkIl-Sung Jang
Nov 8, 2014·British Journal of Pharmacology·Christine M EmnettSteven Mennerick

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Citations

Feb 8, 2011·PloS One·Ben D RichardsonDonald M Caspary
Oct 15, 2008·PloS One·Xiao-Bing ZhangTian-Le Xu
Apr 28, 2004·Trends in Neurosciences·Alexey SemyanovR Angus Silver
Dec 15, 2017·Organic Letters·Wei XiaoYing-Chun Chen

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