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Pentobarbital modulates gamma-aminobutyric acid-activated single-channel conductance in rat cultured hippocampal neurons.
Department of Physiology and Anesthesiology, UCLA School of Medicine.
2000 (English)In: Molecular Pharmacology, ISSN 0026-895X, E-ISSN 1521-0111, Vol. 58, no 3, 463-9 p.Article in journal (Refereed) Published
Abstract [en]

We examined the effect of a range of pentobarbital concentrations on 0.5 microM gamma-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 microM and the data could be fitted by a Hill-type equation. At 100 microM pentobarbital plus 0.5 microM GABA, the conductance seemed to reach a plateau. The pentobarbital EC(50)(0.5 microM GABA) value was 22 +/- 4 microM and n was 1.9 +/- 0.5. In 1 mM pentobarbital plus 0.5 microM GABA, the single-channel conductance decreased to 34 +/- 8 pS. This apparent inhibition of channel conductance was relieved by 1 microM 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 microM) 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.

Place, publisher, year, edition, pages
2000. Vol. 58, no 3, 463-9 p.
National Category
Neurosciences Physiology
URN: urn:nbn:se:uu:diva-182734PubMedID: 10953037OAI: oai:DiVA.org:uu-182734DiVA: diva2:560706
Available from: 2012-10-15 Created: 2012-10-15 Last updated: 2012-10-15

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Birnir, Bryndis
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