Journal article
Potentiation by sevoflurane of the γ‐aminobutyric acid‐induced chloride current in acutely dissociated CA1 pyramidal neurones from rat hippocampus
British journal of pharmacology, Vol.119(5), pp.1013-1021
11/1996
DOI: 10.1111/j.1476-5381.1996.tb15772.x
PMCID: PMC1915958
PMID: 8922750
Abstract
1
The effects of a new kind of volatile anaesthetic, sevoflurane (Sev), on γ‐aminobutyric acid (GABA)‐gated chloride current (IC***1) in single neurones dissociated from the rat hippocampal CA1 area were examined using the nystatin perforated patch recording configuration under the voltage‐clamp condition. All drugs were applied with a rapid perfusion system, termed the ‘Y‐tube’ method.
2
When the concentrations were higher than 3 × 10−4 m, Sev, itself, induced an inward current (Isev) at a holding potential (VH) of −40 mV. The concentration‐response curve of Isev was bell‐shaped, with a suppressed peak and plateau currents at high concentrations (above 2 × 10−3 m). The reversal potential of Isev (Esev) was close to the theoretical Cl− equilibrium potential, indicating that Isev was carried mainly by Cl−.
3
Isev was reversibly blocked by bicuculline (Bic), an antagonist of the GABAA receptor, in a concentration‐dependent manner with a half‐inhibitory concentration (IC50) of 7.2 × 10−7 m. But Iscv was insensitive to strychnine (Str), an antagonist of the glycine receptor.
4
At low concentrations (between 3 × 10−4 and 10−3 m), Sev markedly enhanced the 10−6 m GABA induced current (IGABA) but reduced the IGABA with accelerating desensitization accompanied by a ‘hump’ current after washout at high concentrations (higher than 2 × 10−3 m).
5
Sev, 10−3 m potentiated the current induced by low concentrations of GABA (between 10−7 and 3 × 10−6 m) but reduced the current induced by high concentrations (higher than 10−5 m) of GABA with a clear acceleration of IGABA desensitization.
6
Sev, like pentobarbitone (PB), pregnanolone (PGN) or diazepam (DZP), potentiated the 10−6 m GABA‐induced response without shifting the reversal potential of IGABA.
7
Isev was augmented by PB, PGN, or DZP at concentrations that maximally potentiated IGABA, suggesting that Sev enhanced IGABA at a binding site distinct from that for PB, PGN, or DZP.
8
It is concluded that Sev acts on the GABAA receptor complex mimicking the GABA‐induced chloride current at high concentrations. At low concentrations, Sev enhances GABA‐gated chloride current at a binding site independent of the allosteric modulator sites of barbiturates, benzodiazepines or neurosteroids. The reversible potentiation of the inhibitory GABAA receptor‐mediated Cl− current may result in the depressing of postsynaptic excitability and may, at least in part, underlie the anaesthetic action of Sev.
Details
- Title: Subtitle
- Potentiation by sevoflurane of the γ‐aminobutyric acid‐induced chloride current in acutely dissociated CA1 pyramidal neurones from rat hippocampus
- Creators
- Jie WuNobutoshi HarataNorio Akaike
- Resource Type
- Journal article
- Publication Details
- British journal of pharmacology, Vol.119(5), pp.1013-1021
- Publisher
- Blackwell Publishing Ltd; Oxford, UK
- DOI
- 10.1111/j.1476-5381.1996.tb15772.x
- PMID
- 8922750
- PMCID
- PMC1915958
- ISSN
- 0007-1188
- eISSN
- 1476-5381
- Number of pages
- 9
- Language
- English
- Date published
- 11/1996
- Academic Unit
- Molecular Physiology and Biophysics
- Record Identifier
- 9984025696602771
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