Nanomolar allopregnanolone potentiates rat cerebellar GABAA receptors

doi:10.1016/j.neulet.2005.03.064

Neuroscience Letters

Volume 383, Issues 1–2, 22–29 July 2005, Pages 127-130

https://doi.org/10.1016/j.neulet.2005.03.064 Get rights and content

Abstract

The ionophore function of γ-aminobutyric acid A (GABA_A) receptors was studied by whole-cell patch clamp electrophysiology in primary cultures of rat cerebellar cortex. Chloride currents elicited by 1 μM GABA were potentiated by allopregnanolone with a plateau of high affinity (EC₅₀ = 14 nM) and a peak of potentiation around 1 μM allopregnanolone. Furosemide (0.1 mM) eliminated the high affinity phase and increased the EC₅₀ to 685 nM. GABA_A receptors of rat cerebellar synaptosomal membranes were labelled with [³H]ethynylbicycloorthobenzoate (EBOB). Allopregnanolone displaced [³H]EBOB binding with IC₅₀ = 320 nM. The displacing potency of allopregnanolone was strongly enhanced (IC₅₀ = 39 nM) in the presence of 400 nM GABA and 60 nM SR 95531. Nanomolar potentiation by allopregnanolone can be associated with cerebellar GABA_A receptors containing α₆, β_2–3 and δ subunits. This might be suitable for physiological modulation of tonic inhibitory neurotransmission via extrasynaptic GABA_A receptors in cerebellar granule cells by neurosteroids.

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Acknowledgments

Dr. József Nagy is acknowledged for providing the cell cultures, and Ms. Anikó Kossár and Mrs. Gabriella Auth-Éles for excellent technical assistance. This study was supported by a grant 1/A/005/2004 NKFP MediChem 2.

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Nanomolar allopregnanolone potentiates rat cerebellar GABAA receptors

Abstract

Section snippets

Acknowledgments

Dev. Brain Res.

Neuropharmacology

Neuron

Eur. J. Pharmacol.

Neurosci. Lett.

Neurosci. Lett.

Neurochem. Intern.

Neuroscience

Neurosteroids shift partial agonist activation of GABAA receptor channels from low- to high-efficacy gating patterns

J. Neurosci.

Integration of quanta in cerebellar granule cells during sensory processing

Nature

Role of brain allopregnanolone in the plasticity of γ-aminobutyric acid type A receptor in rat brain during pregnancy and after delivery

Proc. Natl. Acad. Sci. U.S.A.

Variations on an inhibitory theme: phasic and tonic activation of GABAA receptors

Nat. Rev. Neurosci.

Nanomolar allopregnanolone potentiates rat cerebellar GABA_A receptors

Neurosteroids shift partial agonist activation of GABA_A receptor channels from low- to high-efficacy gating patterns

Variations on an inhibitory theme: phasic and tonic activation of GABA_A receptors