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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/4146

Title: Mechanisms for picrotoxinin and picrotin blocks of alpha(2) homomeric glycine receptors
Authors: Wang, Dian-Shi
BUCKINX, Roeland
Lecorronc, Herve
MANGIN, Jean-Marie
RIGO, Jean-Michel
Legendre, Pascal
Issue Date: 2007
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation: JOURNAL OF BIOLOGICAL CHEMISTRY, 282(22). p. 16016-16035
Abstract: Contrary to its effect on the gamma-aminobutyric acid type A and C receptors, picrotoxin antagonism of the alpha(1) homomeric glycine receptors (GlyRs) has been shown to be non-use-dependent and nonselective between the picrotoxin components picrotoxinin and picrotin. Picrotoxin antagonism of the embryonic alpha(2) homomeric GlyR is known to be use-dependent and reflects a channel-blocking mechanism, but the selectivity of picrotoxin antagonism of the embryonic alpha(2) homomeric GlyRs between picrotoxinin and picrotin is unknown. Hence, we used the patch clamp recording technique in the outside-out configuration to investigate, at the single channel level, the mechanism of picrotin- and picrotoxinin-induced inhibition of currents, which were evoked by the activation of alpha(2) homomeric GlyRs stably transfected into Chinese hamster ovary cells. Although both picrotoxinin and picrotin inhibited glycine-evoked outside-out currents, picrotin had a 30 times higher IC50 than picrotoxinin. Picrotin-evoked inhibition displayed voltage dependence, whereas picrotoxinin did not. Picrotoxinin and picrotin decreased the mean open time of the channel in a concentration-dependent manner, indicating that these picrotoxin components can bind to the receptor in its open state. When picrotin and glycine were co-applied, a large rebound current was observed at the end of the application. This rebound current was considerably smaller when picrotoxinin and glycine were co-applied. Both picrotin and picrotoxinin were unable to bind to the unbound conformation of the receptor, but both could be trapped at their binding site when the channel closed during glycine dissociation. Our data indicate that picrotoxinin and picrotin are not equivalent in blocking alpha(2) homomeric GlyR.
Notes: Univ Paris 06, NPA, UKMR 7102, CNRS, F-75252 Paris 05, France. Childrens Natl Med Ctr, Ctr Neurosci Res, Washington, DC 20010 USA. Univ Hasselt, Biomed Res Ctr, B-3590 Diepenbeek, Belgium. Fourth Mil Med Univ, Dept Anat, Xian 710032, Peoples R China.Legendre, P, Univ Paris 06, NPA, UKMR 7102, CNRS, Batiment B,6 Etage,Case 1,9 Quai St, F-75252 Paris 05, France.pascal.legendre@snv.jussieu.fr
URI: http://hdl.handle.net/1942/4146
Link to publication: http://www.jbc.org/cgi/content/abstract/M701502200v1
ISI #: 000246794300010
ISSN: 0021-9258
Category: A1
Type: Journal Contribution
Validation: ecoom, 2008
Appears in Collections: Research publications

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