Isoflurane slows inactivation kinetics of rat recombinant α1β2γ2L GABAA receptors: Enhancement of GABAergic transmission despite an open-channel block

Gerhard Hapfelmeier; Rainer Haseneder; Matthias Eder; Helmuth Adelsberger; Eberhard Kochs; Gerhard Rammes; Walter Zieglgänsberger

doi:10.1016/S0304-3940(01)01950-4

Isoflurane slows inactivation kinetics of rat recombinant α₁β₂γ_2L GABA_A receptors: Enhancement of GABAergic transmission despite an open-channel block

Gerhard Hapfelmeier
, Rainer Haseneder
, Matthias Eder
, Helmuth Adelsberger
, Eberhard Kochs
, Gerhard Rammes
, Walter Zieglgänsberger

Department of Anesthesiology and Intensive Care

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

15 Scopus citations

Abstract

Recombinant α₁β₂γ_2L γ-aminobutyric acid (A) receptor (GABA_AR) channels expressed in human embryonic kidney (HEK293) cells were used for patch-clamp experiments. The currents activated by brief pulses of GABA (10^-4 M) applied with a device for fast solution exchange to cells clamped in the whole-cell configuration mimicked GABA_AR-mediated inhibitory postsynaptic currents. Isoflurane (ISO) at clinically relevant concentrations (0.6 mM) decreased the amplitude and prolonged the decay of the GABA-evoked response. To further detail the mechanism underlying the prolonged decay time, we made simulations based on these measurements. These simulations suggest that ISO slows the rate of GABA unbinding from the receptor. Under these conditions, ISO increases the GABA-induced charge transfer and, thus, could enhance GABAergic inhibition despite the concomitant open-channel block causing the decrease in the current amplitude.

Original language	English
Pages (from-to)	97-100
Number of pages	4
Journal	Neuroscience Letters
Volume	307
Issue number	2
DOIs	https://doi.org/10.1016/S0304-3940(01)01950-4
State	Published - 13 Jul 2001

Keywords

Anesthetics
Channel block
Computer simulations
Isoflurane
Patch-clamp
γ-Aminobutyric acid (A) receptor

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10.1016/S0304-3940(01)01950-4

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title = "Isoflurane slows inactivation kinetics of rat recombinant α1β2γ2L GABAA receptors: Enhancement of GABAergic transmission despite an open-channel block",

abstract = "Recombinant α1β2γ2L γ-aminobutyric acid (A) receptor (GABAAR) channels expressed in human embryonic kidney (HEK293) cells were used for patch-clamp experiments. The currents activated by brief pulses of GABA (10-4 M) applied with a device for fast solution exchange to cells clamped in the whole-cell configuration mimicked GABAAR-mediated inhibitory postsynaptic currents. Isoflurane (ISO) at clinically relevant concentrations (0.6 mM) decreased the amplitude and prolonged the decay of the GABA-evoked response. To further detail the mechanism underlying the prolonged decay time, we made simulations based on these measurements. These simulations suggest that ISO slows the rate of GABA unbinding from the receptor. Under these conditions, ISO increases the GABA-induced charge transfer and, thus, could enhance GABAergic inhibition despite the concomitant open-channel block causing the decrease in the current amplitude.",

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author = "Gerhard Hapfelmeier and Rainer Haseneder and Matthias Eder and Helmuth Adelsberger and Eberhard Kochs and Gerhard Rammes and Walter Zieglg{\"a}nsberger",

year = "2001",

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doi = "10.1016/S0304-3940(01)01950-4",

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AU - Hapfelmeier, Gerhard

AU - Haseneder, Rainer

AU - Eder, Matthias

AU - Adelsberger, Helmuth

AU - Kochs, Eberhard

AU - Rammes, Gerhard

AU - Zieglgänsberger, Walter

PY - 2001/7/13

Y1 - 2001/7/13

N2 - Recombinant α1β2γ2L γ-aminobutyric acid (A) receptor (GABAAR) channels expressed in human embryonic kidney (HEK293) cells were used for patch-clamp experiments. The currents activated by brief pulses of GABA (10-4 M) applied with a device for fast solution exchange to cells clamped in the whole-cell configuration mimicked GABAAR-mediated inhibitory postsynaptic currents. Isoflurane (ISO) at clinically relevant concentrations (0.6 mM) decreased the amplitude and prolonged the decay of the GABA-evoked response. To further detail the mechanism underlying the prolonged decay time, we made simulations based on these measurements. These simulations suggest that ISO slows the rate of GABA unbinding from the receptor. Under these conditions, ISO increases the GABA-induced charge transfer and, thus, could enhance GABAergic inhibition despite the concomitant open-channel block causing the decrease in the current amplitude.

AB - Recombinant α1β2γ2L γ-aminobutyric acid (A) receptor (GABAAR) channels expressed in human embryonic kidney (HEK293) cells were used for patch-clamp experiments. The currents activated by brief pulses of GABA (10-4 M) applied with a device for fast solution exchange to cells clamped in the whole-cell configuration mimicked GABAAR-mediated inhibitory postsynaptic currents. Isoflurane (ISO) at clinically relevant concentrations (0.6 mM) decreased the amplitude and prolonged the decay of the GABA-evoked response. To further detail the mechanism underlying the prolonged decay time, we made simulations based on these measurements. These simulations suggest that ISO slows the rate of GABA unbinding from the receptor. Under these conditions, ISO increases the GABA-induced charge transfer and, thus, could enhance GABAergic inhibition despite the concomitant open-channel block causing the decrease in the current amplitude.

KW - Anesthetics

KW - Channel block

KW - Computer simulations

KW - Isoflurane

KW - Patch-clamp

KW - γ-Aminobutyric acid (A) receptor

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DO - 10.1016/S0304-3940(01)01950-4

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SN - 0304-3940

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JO - Neuroscience Letters

JF - Neuroscience Letters

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ER -

Isoflurane slows inactivation kinetics of rat recombinant α₁β₂γ_2L GABA_A receptors: Enhancement of GABAergic transmission despite an open-channel block

Abstract

Keywords

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