Kinetic analysis of voltage-dependent potentiation and block of the glycine alpha 3 receptor by a neuroactive steroid analogue.

The Journal of Physiology
Xiaochun JinJoe Henry Steinbach

Abstract

We examined the actions of a carboxylated analogue of pregnanolone ((3alpha,5beta)-20-oxopregnane-3-carboxylic acid; 3alphaCOOH5betaP) on receptors composed of glycine receptor alpha3 subunits, expressed in Xenopus oocytes. This analogue both inhibits and potentiates this receptor; potentiation increases with more negative membrane potentials while block increases with less negative membrane potentials. We used a second analogue ((3alpha,5beta)-3-hydroxymethylpregnan-20-one; 3alphaCH(2)OH5betaP) to examine the mechanism for voltage-dependent potentiation. This analogue potentiates but does not block the glycine alpha3 receptor. Steady-state responses and current relaxations following voltage jumps support the idea that the voltage dependence of potentiation indirectly arises from a voltage dependence for channel activation by glycine, rather than an intrinsic voltage dependence for potentiation. Potentiation results from a slowing of the channel deactivation rate. In the absence of steroid, at a low [glycine] current relaxations after a voltage jump show two exponential components, with a weighted average time constant of approximately 425 ms (-50 mV, 22 degrees C). The rate for channel deactivation increases at more negative p...Continue Reading

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Citations

Nov 13, 2012·Molecular Pharmacology·Andrew J LinsenbardtSteven Mennerick
Nov 29, 2012·The Journal of Clinical Investigation·Irene LeckerBeverley A Orser
Apr 1, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Xiaochun Jin, Joe Henry Steinbach
Dec 10, 2013·Psychopharmacology·Megan M EatonGustav Akk
Apr 25, 2013·The Journal of Physiology·Alessandro MarabelliLucia G Sivilotti
Oct 23, 2012·Neuroscience and Biobehavioral Reviews·Charles F ZorumskiSteven Mennerick
May 12, 2011·British Journal of Pharmacology·Gonzalo E Yevenes, Hanns Ulrich Zeilhofer
May 18, 2018·International Journal of Neural Systems·Marie-Constance CorsiFabrizio De Vico Fallani
Mar 23, 2021·Biological Chemistry·Ulrike BreitingerHans-Georg Breitinger

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