The monomers, oligomers, and fibrils of amyloid-β inhibit the activity of mitoBK Ca channels by a membrane-mediated mechanism.

Autor: Kravenska Y; Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology PAS, Pasteura str. 3, Warsaw 02-093, Poland; Department of Biophysics of Ion Channels, Bogomoletz Institute of Physiology NASU, Bogomoletz str. 4, Kyiv 01-024, Ukraine. Electronic address: y.kravenska@nencki.edu.pl., Nieznanska H; Laboratory of Electron Microscopy, Nencki Institute of Experimental Biology PAS, Pasteura str. 3, Warsaw 02-093, Poland., Nieznanski K; Laboratory of Molecular Basis of Cell Motility, Nencki Institute of Experimental Biology PAS, Pasteura str. 3, Warsaw 02-093, Poland., Lukyanetz E; Department of Biophysics of Ion Channels, Bogomoletz Institute of Physiology NASU, Bogomoletz str. 4, Kyiv 01-024, Ukraine., Szewczyk A; Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology PAS, Pasteura str. 3, Warsaw 02-093, Poland., Koprowski P; Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology PAS, Pasteura str. 3, Warsaw 02-093, Poland.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Biomembranes [Biochim Biophys Acta Biomembr] 2020 Sep 01; Vol. 1862 (9), pp. 183337. Date of Electronic Publication: 2020 May 04.
DOI: 10.1016/j.bbamem.2020.183337
Abstrakt: A causative agent of Alzheimer's disease (AD) is a short amphipathic peptide called amyloid beta (Aβ). Aβ monomers undergo structural changes leading to their oligomerization or fibrillization. The monomers as well as all aggregated forms of Aβ, i.e., oligomers, and fibrils, can bind to biological membranes, thereby modulating membrane mechanical properties. It is also known that some isoforms of the large-conductance calcium-activated potassium (BK Ca ) channel, including the mitochondrial BK Ca (mitoBK Ca ) channel, respond to mechanical changes in the membrane. Here, using the patch-clamp technique, we investigated the impact of full-length Aβ (Aβ 1 - 42 ) and its fragment, Aβ 25 - 35 , on the activity of mitoBK Ca channels. We found that all forms of Aβ inhibited the activity of the mitoBK Ca channel in a concentration-dependent manner. Since monomers, oligomers, and fibrils of Aβ exhibit different molecular characteristics and structures, we hypothesized that the inhibition was not due to direct peptide-protein interactions but rather to membrane-binding of the Aβ peptides. Our findings supported this hypothesis by showing that Aβ peptides block mitoBK Ca channels irrespective of the side of the membrane to which they are applied. In addition, we found that the enantiomeric peptide, D-Aβ 1 - 42 , demonstrated similar inhibitory activity towards mitoBK Ca channels. As a result, we proposed a general model in which all Aβ forms i.e., monomers, oligomers, and amyloid fibrils, contribute to the progression of AD by exerting a modulatory effect on mechanosensitive membrane components.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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