Common Binding Site for Externally and Internally Applied AMPA Receptor Channel Blockers

Adamantane derivative IEM-1676 (Ad-N + H 2 -(CH 2 ) 5 -N + Me 3 ) causes open-channel block of Ca 2+ -permeable AMPA receptors when applied externally, but internal application results in both closed- and open-channel block. The relationships between blocking action of externally and internally appl...

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Bibliographic Details
Published in:Journal of molecular neuroscience 2009-09, Vol.39 (1-2), p.169-174
Main Authors: Tikhonova, Tatyana B., Tikhonov, Denis B., Magazanik, Lev G.
Format: Article
Language:English
Subjects:
Adamantane - analogs & derivatives
Adamantane - pharmacology
Animals
Binding Sites
Biomedical and Life Sciences
Biomedicine
Brief Communication
Cell Biology
Ion Channel Gating - drug effects
Neurochemistry
Neurology
Neurosciences
Patch-Clamp Techniques
Proteomics
Rats
Rats, Wistar
Receptors, AMPA - antagonists & inhibitors
Receptors, AMPA - metabolism
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Summary:Adamantane derivative IEM-1676 (Ad-N + H 2 -(CH 2 ) 5 -N + Me 3 ) causes open-channel block of Ca 2+ -permeable AMPA receptors when applied externally, but internal application results in both closed- and open-channel block. The relationships between blocking action of externally and internally applied IEM-1676 were studied using patch clamp technique. Extracellular action of IEM-1676 was decreased by its intracellular application, thus suggesting that the binding sites of the externally and internally applied drug coincide or at least overlap significantly. We demonstrated that internal closed-channel block is voltage-dependent and occurs at the region where the externally applied drug is trapped. We conclude that the selectivity filter of the closed AMPA receptor channel is not occluded and remains permeable for organic cations.
ISSN:0895-8696
1559-1166
DOI:10.1007/s12031-008-9172-5