Cyclodextrins Exert a Ligand-like Current Inhibitory Effect on the KV1.3 Ion Channel Independent of Membrane Cholesterol Extraction

Cyclodextrins (CDs) are cyclic oligosaccharides capable of forming water-soluble complexes with a variety of otherwise poorly soluble molecules including cholesterol and different drugs. Consistently, CDs are widely used in research and clinical practice to deplete cholesterol from cellular membrane...

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Autores principales:	Tamas Kovacs, Tamas Sohajda, Lajos Szente, Peter Nagy, Gyorgy Panyi, Zoltan Varga, Florina Zakany
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	cyclodextrin cholesterol membrane fluidity membrane hydration membrane lipid order ligand-like interaction Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4110892c186142c0976828cc585642e4
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spelling	oai:doaj.org-article:4110892c186142c0976828cc585642e42021-11-04T05:49:09ZCyclodextrins Exert a Ligand-like Current Inhibitory Effect on the KV1.3 Ion Channel Independent of Membrane Cholesterol Extraction2296-889X10.3389/fmolb.2021.735357https://doaj.org/article/4110892c186142c0976828cc585642e42021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.735357/fullhttps://doaj.org/toc/2296-889XCyclodextrins (CDs) are cyclic oligosaccharides capable of forming water-soluble complexes with a variety of otherwise poorly soluble molecules including cholesterol and different drugs. Consistently, CDs are widely used in research and clinical practice to deplete cholesterol from cellular membranes or to increase solubility and bioavailability of different pharmaceuticals at local concentrations in the millimolar range. Effects of CDs exerted on cellular functions are generally thought to originate from reductions in cholesterol levels. Potential direct, ligand-like CD effects are largely neglected in spite of several recent studies reporting direct interaction between CDs and proteins including AMP-activated protein kinase, β-amyloid peptides, and α-synuclein. In this study, by using patch-clamp technique, time-resolved quantitation of cholesterol levels and biophysical parameters and applying cholesterol-extracting and non-cholesterol-extracting CDs at 1 and 5 mM concentrations, we provide evidence for a previously unexplored ligand-like, cholesterol-independent current inhibitory effect of CDs on KV1.3, a prototypical voltage-gated potassium channel with pathophysiological relevance in various autoimmune and neurodegenerative disorders. Our findings propose that potential direct CD effects on KV channels should be taken into consideration when interpreting functional consequences of CD treatments in both research and clinical practice. Furthermore, current-blocking effects of CDs on KV channels at therapeutically relevant concentrations might contribute to additional beneficial or adverse effects during their therapeutic applications.Tamas KovacsTamas SohajdaLajos SzentePeter NagyGyorgy PanyiZoltan VargaFlorina ZakanyFrontiers Media S.A.articlecyclodextrincholesterolmembrane fluiditymembrane hydrationmembrane lipid orderligand-like interactionBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cyclodextrin cholesterol membrane fluidity membrane hydration membrane lipid order ligand-like interaction Biology (General) QH301-705.5
spellingShingle	cyclodextrin cholesterol membrane fluidity membrane hydration membrane lipid order ligand-like interaction Biology (General) QH301-705.5 Tamas Kovacs Tamas Sohajda Lajos Szente Peter Nagy Gyorgy Panyi Zoltan Varga Florina Zakany Cyclodextrins Exert a Ligand-like Current Inhibitory Effect on the KV1.3 Ion Channel Independent of Membrane Cholesterol Extraction
description	Cyclodextrins (CDs) are cyclic oligosaccharides capable of forming water-soluble complexes with a variety of otherwise poorly soluble molecules including cholesterol and different drugs. Consistently, CDs are widely used in research and clinical practice to deplete cholesterol from cellular membranes or to increase solubility and bioavailability of different pharmaceuticals at local concentrations in the millimolar range. Effects of CDs exerted on cellular functions are generally thought to originate from reductions in cholesterol levels. Potential direct, ligand-like CD effects are largely neglected in spite of several recent studies reporting direct interaction between CDs and proteins including AMP-activated protein kinase, β-amyloid peptides, and α-synuclein. In this study, by using patch-clamp technique, time-resolved quantitation of cholesterol levels and biophysical parameters and applying cholesterol-extracting and non-cholesterol-extracting CDs at 1 and 5 mM concentrations, we provide evidence for a previously unexplored ligand-like, cholesterol-independent current inhibitory effect of CDs on KV1.3, a prototypical voltage-gated potassium channel with pathophysiological relevance in various autoimmune and neurodegenerative disorders. Our findings propose that potential direct CD effects on KV channels should be taken into consideration when interpreting functional consequences of CD treatments in both research and clinical practice. Furthermore, current-blocking effects of CDs on KV channels at therapeutically relevant concentrations might contribute to additional beneficial or adverse effects during their therapeutic applications.
format	article
author	Tamas Kovacs Tamas Sohajda Lajos Szente Peter Nagy Gyorgy Panyi Zoltan Varga Florina Zakany
author_facet	Tamas Kovacs Tamas Sohajda Lajos Szente Peter Nagy Gyorgy Panyi Zoltan Varga Florina Zakany
author_sort	Tamas Kovacs
title	Cyclodextrins Exert a Ligand-like Current Inhibitory Effect on the KV1.3 Ion Channel Independent of Membrane Cholesterol Extraction
title_short	Cyclodextrins Exert a Ligand-like Current Inhibitory Effect on the KV1.3 Ion Channel Independent of Membrane Cholesterol Extraction
title_full	Cyclodextrins Exert a Ligand-like Current Inhibitory Effect on the KV1.3 Ion Channel Independent of Membrane Cholesterol Extraction
title_fullStr	Cyclodextrins Exert a Ligand-like Current Inhibitory Effect on the KV1.3 Ion Channel Independent of Membrane Cholesterol Extraction
title_full_unstemmed	Cyclodextrins Exert a Ligand-like Current Inhibitory Effect on the KV1.3 Ion Channel Independent of Membrane Cholesterol Extraction
title_sort	cyclodextrins exert a ligand-like current inhibitory effect on the kv1.3 ion channel independent of membrane cholesterol extraction
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4110892c186142c0976828cc585642e4
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Cyclodextrins Exert a Ligand-like Current Inhibitory Effect on the KV1.3 Ion Channel Independent of Membrane Cholesterol Extraction

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