Document Detail

Interaction between cyclodextrin and neuronal membrane results in modulation of GABA(A) receptor conformational transitions.
MedLine Citation:
PMID:  16702996     Owner:  NLM     Status:  MEDLINE    
Cyclodextrins (CDs) are nanostructures widely applied in biotechnology and chemistry. Owing to partially hydrophobic character, CDs interact with biological membranes. While the mechanisms of CDs interactions with lipids were widely studied, their effects on proteins are less understood. In the present study we investigated the effects of beta cyclodextrin (betaCD) on GABA(A) receptor (GABA(A)R) gating. To reliably resolve the kinetics of conformational transitions, currents were elicited by ultrafast gamma-aminobutyric acid (GABA) applications to outside-out patches from rat cultured hippocampal neurons. betaCD increased the amplitude of responses to saturating GABA concentration ([GABA]) in a dose-dependent manner and this effect was accompanied by profound alterations in the current kinetics. Current deactivation was slowed down by betaCD but this effect was biphasic with a maximum at around 0.5 mM betaCD. While the fast deactivation time constant was monotonically slowed down within considered betaCD concentration range, the slow component first increased and then, at millimolar betaCD concentration, decreased. The rate and extent of desensitization was decreased by betaCD in a dose-dependent manner. The analysis of current responses to nonsaturating [GABA] indicated that betaCD affected the GABA(A)R agonist binding site by slowing down the unbinding rate. Modulation of GABA(A)R desensitization and binding showed different concentration-dependence suggesting different modualtory sites with higher affinity of the latter one. All the betaCD effects were fully reversible indicating that cholesterol uptake into betaCD was not the primary mechanism. We conclude that betaCD is a strong modulator of GABA(A)R conformational transitions.
Maria Pytel; Katarzyna Mercik; Jerzy W Mozrzymas
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-05-15
Journal Detail:
Title:  British journal of pharmacology     Volume:  148     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-12     Completed Date:  2006-08-16     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  413-22     Citation Subset:  IM    
Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, Poland.
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MeSH Terms
Binding Sites
Cell Membrane / drug effects
Cells, Cultured
Hippocampus / drug effects
Neurons / drug effects
Protein Conformation
Rats, Wistar
Receptors, GABA-A / chemistry,  drug effects*
beta-Cyclodextrins / pharmacology*
Reg. No./Substance:
0/Receptors, GABA-A; 0/beta-Cyclodextrins; JV039JZZ3A/betadex

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