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Penicillin blocks human alpha 1 beta 1 and alpha 1 beta 1 gamma 2S GABAA channels that open spontaneously.
Molecular and Cellular Physiology, Department of Physiological Sciences, Lund University.
2004 (English)In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 496, no 1-3, 23-32 p.Article in journal (Refereed) Published
Abstract [en]

We used the open-channel blocker, penicillin (10 mM), as a tool to investigate if the human alpha1beta1 or alpha1beta1gamma2S gamma-aminobutyric acid type A (GABAA) receptor channels opened in the absence of GABA. Application of penicillin to cells expressing the receptors resulted in a transient inward whole-cell current, the off-current, upon penicillin removal. The amplitude of the off-current was dependent on the duration of the penicillin application, it reversed in polarity at depolarized potentials and exhibited "run-down" similar to the GABA-activated currents. Bicuculline (100 microM) blocked the off-current response. Pentobarbital (50 microM) enhanced the peak off-current amplitude by 2.8 and 3.4 in alpha1beta1 and alpha1beta1gamma2S receptors, respectively. Diazepam (1 microM) only enhanced the off-current peak response in alpha1beta1gamma2S receptors (1.6) and induced the development of an inward current when applied alone. The results are consistent with that the alpha1beta1 or alpha1beta1gamma2) GABAA receptors can open in the absence of GABA and raise the question of what role spontaneous channel openings have in the function of GABAA receptors.

Place, publisher, year, edition, pages
2004. Vol. 496, no 1-3, 23-32 p.
National Category
Physiology
Identifiers
URN: urn:nbn:se:uu:diva-182709DOI: 10.1016/j.ejphar.2004.06.004PubMedID: 15288571OAI: oai:DiVA.org:uu-182709DiVA: diva2:560613
Available from: 2012-10-15 Created: 2012-10-15 Last updated: 2017-12-07

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