Physiological modulation of the GABA receptor by convulsant and anticonvulsant barbiturates in cultured rat hippocampal neurons

Katherine D. Holland; Daniel J. Canney; Steven M. Rothman; J. A. Ferrendelli; Douglas F. Covey

doi:10.1016/0006-8993(90)90910-4

Physiological modulation of the GABA receptor by convulsant and anticonvulsant barbiturates in cultured rat hippocampal neurons

Katherine D. Holland, Daniel J. Canney, Steven M. Rothman, J. A. Ferrendelli, Douglas F. Covey

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

13 Scopus citations

Abstract

The actions of convulsant and sedative barbiturates on responses to γ-aminobutyric acid (GABA) application and on inhibitory postsynaptic currents were compared using voltage-clamp techniques in cultured rat hippocampal neurons. The convulsant barbiturates, 5-ethyl-5-(3-methylbut-2-enyl) barbituric acid (3M2B), and (+)-5-ethyl-5-(1,3-dimethylbutyl) barbituric acid ((+)-DMBB), and the sedative barbiturate, 5-ethyl-5-(3-methylbutyl) barbituric acid (3MB), all potentiated GABA-mediated chloride currents. In addition, these compounds prolonged the duration of GABAergic inhibitory postsynaptic currents. The similarity between the action of convulsant and sedative barbiturates suggests that the convulsant activity of 3M2B and (+)-DMBB are not mediated by their actions at GABAergic synapses.

Original language	English
Pages (from-to)	147-150
Number of pages	4
Journal	Brain Research
Volume	516
Issue number	1
DOIs	https://doi.org/10.1016/0006-8993(90)90910-4
State	Published - May 14 1990

Keywords

Barbiturate
Convulsant
Inhibitory synapse
Voltage-clamp
γ-Aminobutyric acid

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10.1016/0006-8993(90)90910-4

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@article{d963cd1b46c146bbbf3814b7b17bd74c,

title = "Physiological modulation of the GABA receptor by convulsant and anticonvulsant barbiturates in cultured rat hippocampal neurons",

abstract = "The actions of convulsant and sedative barbiturates on responses to γ-aminobutyric acid (GABA) application and on inhibitory postsynaptic currents were compared using voltage-clamp techniques in cultured rat hippocampal neurons. The convulsant barbiturates, 5-ethyl-5-(3-methylbut-2-enyl) barbituric acid (3M2B), and (+)-5-ethyl-5-(1,3-dimethylbutyl) barbituric acid ((+)-DMBB), and the sedative barbiturate, 5-ethyl-5-(3-methylbutyl) barbituric acid (3MB), all potentiated GABA-mediated chloride currents. In addition, these compounds prolonged the duration of GABAergic inhibitory postsynaptic currents. The similarity between the action of convulsant and sedative barbiturates suggests that the convulsant activity of 3M2B and (+)-DMBB are not mediated by their actions at GABAergic synapses.",

keywords = "Barbiturate, Convulsant, Inhibitory synapse, Voltage-clamp, γ-Aminobutyric acid",

author = "Holland, {Katherine D.} and Canney, {Daniel J.} and Rothman, {Steven M.} and Ferrendelli, {J. A.} and Covey, {Douglas F.}",

note = "Funding Information: We would like to thank Nancy Lancaster for culture preparation and Kelvin Yamada for help in preparation of the manuscript. Assistance was also provided by the Washington University High Resolution NMR facility (supported in part by NIH 1 S10 RR00204 and a gift from the Monsanto Co.). This work was supported by NIH Grant GM 07805, NS 07129, NS 14834 and NS 19988.",

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doi = "10.1016/0006-8993(90)90910-4",

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AU - Holland, Katherine D.

AU - Canney, Daniel J.

AU - Rothman, Steven M.

AU - Ferrendelli, J. A.

AU - Covey, Douglas F.

N1 - Funding Information: We would like to thank Nancy Lancaster for culture preparation and Kelvin Yamada for help in preparation of the manuscript. Assistance was also provided by the Washington University High Resolution NMR facility (supported in part by NIH 1 S10 RR00204 and a gift from the Monsanto Co.). This work was supported by NIH Grant GM 07805, NS 07129, NS 14834 and NS 19988.

PY - 1990/5/14

Y1 - 1990/5/14

N2 - The actions of convulsant and sedative barbiturates on responses to γ-aminobutyric acid (GABA) application and on inhibitory postsynaptic currents were compared using voltage-clamp techniques in cultured rat hippocampal neurons. The convulsant barbiturates, 5-ethyl-5-(3-methylbut-2-enyl) barbituric acid (3M2B), and (+)-5-ethyl-5-(1,3-dimethylbutyl) barbituric acid ((+)-DMBB), and the sedative barbiturate, 5-ethyl-5-(3-methylbutyl) barbituric acid (3MB), all potentiated GABA-mediated chloride currents. In addition, these compounds prolonged the duration of GABAergic inhibitory postsynaptic currents. The similarity between the action of convulsant and sedative barbiturates suggests that the convulsant activity of 3M2B and (+)-DMBB are not mediated by their actions at GABAergic synapses.

AB - The actions of convulsant and sedative barbiturates on responses to γ-aminobutyric acid (GABA) application and on inhibitory postsynaptic currents were compared using voltage-clamp techniques in cultured rat hippocampal neurons. The convulsant barbiturates, 5-ethyl-5-(3-methylbut-2-enyl) barbituric acid (3M2B), and (+)-5-ethyl-5-(1,3-dimethylbutyl) barbituric acid ((+)-DMBB), and the sedative barbiturate, 5-ethyl-5-(3-methylbutyl) barbituric acid (3MB), all potentiated GABA-mediated chloride currents. In addition, these compounds prolonged the duration of GABAergic inhibitory postsynaptic currents. The similarity between the action of convulsant and sedative barbiturates suggests that the convulsant activity of 3M2B and (+)-DMBB are not mediated by their actions at GABAergic synapses.

KW - Barbiturate

KW - Convulsant

KW - Inhibitory synapse

KW - Voltage-clamp

KW - γ-Aminobutyric acid

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Physiological modulation of the GABA receptor by convulsant and anticonvulsant barbiturates in cultured rat hippocampal neurons

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Keywords

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