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Rapid CommunicationAccelerated Communication

Pentobarbital Modulates γ-Aminobutyric Acid-Activated Single-Channel Conductance in Rat Cultured Hippocampal Neurons

Mansoureh Eghbali, Peter W. Gage and Bryndis Birnir
Molecular Pharmacology September 2000, 58 (3) 463-469; DOI: https://doi.org/10.1124/mol.58.3.463
Mansoureh Eghbali
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Bryndis Birnir
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Abstract

We examined the effect of a range of pentobarbital concentrations on 0.5 μM γ-aminobutyric acid (GABA)-activated channels (10 ± 1 pS) in inside-out or outside-out patches from rat cultured hippocampal neurons. The conductance increased from 12 ± 4 to 62 ± 9 pS as the pentobarbital concentration was raised from 10 to 500 μM and the data could be fitted by a Hill-type equation. At 100 μM pentobarbital plus 0.5 μM GABA, the conductance seemed to reach a plateau. The pentobarbital EC50 0.5 μ M GABA value was 22 ± 4 μM and n was 1.9 ± 0.5. In 1 mM pentobarbital plus 0.5 μM GABA, the single-channel conductance decreased to 34 ± 8 pS. This apparent inhibition of channel conductance was relieved by 1 μM diazepam. The channel conductance was 64 ± 6 pS in the presence of all three drugs. The channels were open more in the presence of both GABA and pentobarbital than in the presence of either drug alone. Pentobarbital alone (100 μM) activated channels with conductance (30 ± 2 pS) and kinetic properties distinct from those activated by either GABA alone or GABA plus pentobarbital. Whether pentobarbital induces new conformations or promotes conformations observed in the presence of GABA alone cannot be determined from our study, but the results clearly show that it is the combination of drugs present that determines the single-channel conductance and the kinetic properties of the receptors.

Footnotes

    • Received February 28, 2000.
    • Accepted May 26, 2000.
  • Send reprint requests to: Dr. Bryndis Birnir, Cell and Molecular Physiology, Dept. of Physiological Sciences, Lund University, Sölvegatan 19, S-223 62 Lund, Sweden. E-mail:bryndis.birnir{at}mphy.lu.se

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Molecular Pharmacology: 58 (3)
Molecular Pharmacology
Vol. 58, Issue 3
1 Sep 2000
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Rapid CommunicationAccelerated Communication

Pentobarbital Modulates γ-Aminobutyric Acid-Activated Single-Channel Conductance in Rat Cultured Hippocampal Neurons

Mansoureh Eghbali, Peter W. Gage and Bryndis Birnir
Molecular Pharmacology September 1, 2000, 58 (3) 463-469; DOI: https://doi.org/10.1124/mol.58.3.463

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Rapid CommunicationAccelerated Communication

Pentobarbital Modulates γ-Aminobutyric Acid-Activated Single-Channel Conductance in Rat Cultured Hippocampal Neurons

Mansoureh Eghbali, Peter W. Gage and Bryndis Birnir
Molecular Pharmacology September 1, 2000, 58 (3) 463-469; DOI: https://doi.org/10.1124/mol.58.3.463
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