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• W1566202711 abstract "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 ( β CD) 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. β CD 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 β CD but this effect was biphasic with a maximum at around 0.5 m M β CD. While the fast deactivation time constant was monotonically slowed down within considered β CD concentration range, the slow component first increased and then, at millimolar β CD concentration, decreased. The rate and extent of desensitization was decreased by β CD in a dose‐dependent manner. The analysis of current responses to nonsaturating [GABA] indicated that β CD 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 β CD effects were fully reversible indicating that cholesterol uptake into β CD was not the primary mechanism. We conclude that β CD is a strong modulator of GABA A R conformational transitions. British Journal of Pharmacology (2006) 148 , 413–422. doi: 10.1038/sj.bjp.0706747" @default.
• W1566202711 created "2016-06-24" @default.
• W1566202711 creator A5046852033 @default.
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• W1566202711 date "2006-06-01" @default.
• W1566202711 modified "2023-10-17" @default.
• W1566202711 title "Interaction between cyclodextrin and neuronal membrane results in modulation of GABA_A receptor conformational transitions" @default.
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• W1566202711 doi "https://doi.org/10.1038/sj.bjp.0706747" @default.
• W1566202711 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1751786" @default.
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