Neurosteroids act on recombinant human GABAA receptors

Giulia Puia; Maria Rita Santi; Stefano Vicini; Dolan B. Pritchett; Robert H. Purdy; Steven M. Paul; Peter H. Seeburg; Erminio Costa

doi:10.1016/0896-6273(90)90202-Q

Neurosteroids act on recombinant human GABA_A receptors

Giulia Puia, Maria Rita Santi, Stefano Vicini, Dolan B. Pritchett, Robert H. Purdy, Steven M. Paul, Peter H. Seeburg, Erminio Costa

Washington University School of Medicine

Research output: Contribution to journal › Article › peer-review

547 Scopus citations

Abstract

The endogenous steroid metabolites 3α,21dihydroxy-5α-pregnan-20-one and 3α-hydroxy-5α-pregnan-20-one potentiate GABA-activated Cl^- currents recorded from a human cell line transfected with the β₁, α₁β₁, and α₁β₁γ₂ combinations of human GABA_A receptor subunits. These steroids are active at nanomolar concentrations in potentiating GABA-activated Cl^- currents and directly elicit bicuculline-sensitive C^- currents when applied at micromolar concentrations. The potentiating and direct actions of both steroids were expressed with every combination of subunits tested. However, an examination of single-channel currents recorded from outside-out patches excised from these transfected cells suggests that despite the common minimal structural requirements for expressing steroid and barbiturate actions, the mechanism of GABA_A receptor modulation by these pregnane steroids may differ from that of barbiturates.

Original language	English
Pages (from-to)	759-765
Number of pages	7
Journal	Neuron
Volume	4
Issue number	5
DOIs	https://doi.org/10.1016/0896-6273(90)90202-Q
State	Published - May 1990

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title = "Neurosteroids act on recombinant human GABAA receptors",

abstract = "The endogenous steroid metabolites 3α,21dihydroxy-5α-pregnan-20-one and 3α-hydroxy-5α-pregnan-20-one potentiate GABA-activated Cl- currents recorded from a human cell line transfected with the β1, α1β1, and α1β1γ2 combinations of human GABAA receptor subunits. These steroids are active at nanomolar concentrations in potentiating GABA-activated Cl- currents and directly elicit bicuculline-sensitive C- currents when applied at micromolar concentrations. The potentiating and direct actions of both steroids were expressed with every combination of subunits tested. However, an examination of single-channel currents recorded from outside-out patches excised from these transfected cells suggests that despite the common minimal structural requirements for expressing steroid and barbiturate actions, the mechanism of GABAA receptor modulation by these pregnane steroids may differ from that of barbiturates.",

author = "Giulia Puia and Santi, {Maria Rita} and Stefano Vicini and Pritchett, {Dolan B.} and Purdy, {Robert H.} and Paul, {Steven M.} and Seeburg, {Peter H.} and Erminio Costa",

year = "1990",

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doi = "10.1016/0896-6273(90)90202-Q",

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T1 - Neurosteroids act on recombinant human GABAA receptors

AU - Puia, Giulia

AU - Santi, Maria Rita

AU - Vicini, Stefano

AU - Pritchett, Dolan B.

AU - Purdy, Robert H.

AU - Paul, Steven M.

AU - Seeburg, Peter H.

AU - Costa, Erminio

PY - 1990/5

Y1 - 1990/5

N2 - The endogenous steroid metabolites 3α,21dihydroxy-5α-pregnan-20-one and 3α-hydroxy-5α-pregnan-20-one potentiate GABA-activated Cl- currents recorded from a human cell line transfected with the β1, α1β1, and α1β1γ2 combinations of human GABAA receptor subunits. These steroids are active at nanomolar concentrations in potentiating GABA-activated Cl- currents and directly elicit bicuculline-sensitive C- currents when applied at micromolar concentrations. The potentiating and direct actions of both steroids were expressed with every combination of subunits tested. However, an examination of single-channel currents recorded from outside-out patches excised from these transfected cells suggests that despite the common minimal structural requirements for expressing steroid and barbiturate actions, the mechanism of GABAA receptor modulation by these pregnane steroids may differ from that of barbiturates.

AB - The endogenous steroid metabolites 3α,21dihydroxy-5α-pregnan-20-one and 3α-hydroxy-5α-pregnan-20-one potentiate GABA-activated Cl- currents recorded from a human cell line transfected with the β1, α1β1, and α1β1γ2 combinations of human GABAA receptor subunits. These steroids are active at nanomolar concentrations in potentiating GABA-activated Cl- currents and directly elicit bicuculline-sensitive C- currents when applied at micromolar concentrations. The potentiating and direct actions of both steroids were expressed with every combination of subunits tested. However, an examination of single-channel currents recorded from outside-out patches excised from these transfected cells suggests that despite the common minimal structural requirements for expressing steroid and barbiturate actions, the mechanism of GABAA receptor modulation by these pregnane steroids may differ from that of barbiturates.

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EP - 765

JO - Neuron

JF - Neuron

IS - 5

ER -

Neurosteroids act on recombinant human GABA_A receptors

Abstract

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