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Protons inhibit Cl- conductance by direct or allosteric interaction with the GABA-binding site in the rat recombinant alpha(1)beta(2)gamma(2L) and alpha(1)beta(2) GABA(A) receptor
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
2005 (English)In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 528, no 1-3, 1-6 p.Article in journal (Refereed) PublishedText
Abstract [en]

Functional roles of external pH on the Cl- conductance were examined on Xenopus oocytes expressing rat recombinant alpha(1)beta(2)gamma(2L) and alpha(1)beta(2) GABA(A) receptors. Acidic pH inhibited GABA-response in a reversible and concentration-dependent manner, significantly increasing the EC50 without appreciably changing the slope or maximal currents induced by GABA in the alpha(1)beta(2)gamma(2L) and alpha(1)beta(2) receptors. In contrast, protonation did not influence the pentobarbital-gated Currents in the alpha(1)beta(2)gamma(2L) receptors, suggesting that protons do not modulate channel activity by directly affecting the channel gating process. Protons competitively inhibited the bicuculline-induced antagonism on GABA in the alpha(1)beta(2)gamma(2L) receptors. The data support the hypothesis that protons inhibit GABA(A) receptor function by direct or allosteric interaction with the GABA-binding site.

Place, publisher, year, edition, pages
Amsterdam: Elsevier, 2005. Vol. 528, no 1-3, 1-6 p.
Keyword [en]
proton, GABA, pentobarbital, GABA(A) receptor, Xenopus oocyte
National Category
Pharmacology and Toxicology Social and Clinical Pharmacy
Identifiers
URN: urn:nbn:se:umu:diva-120390DOI: 10.1016/j.ejphar.2005.11.001ISI: 000234134000001PubMedID: 16325175OAI: oai:DiVA.org:umu-120390DiVA: diva2:937528
Available from: 2016-06-15 Created: 2016-05-16 Last updated: 2016-06-15Bibliographically approved

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Wang, Ming-DeRahman, MoziburZhu, Di
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ReferencesLink to record
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