Please use this identifier to cite or link to this item:
https://hdl.handle.net/11147/10241
Title: | Altered conductance and permeability of Cx40 mutations associated with atrial fibrillation | Authors: | Cruz, Ana Santa Meşe, Gülistan Valiuniene, Laima Brink, Peter R White, Thomas W. Valiunas, Virginijus |
Publisher: | Rockefeller University Press | Abstract: | Gap junctions ensure the rapid propagation of the action potential throughout the myocardium. Three mutant forms of connexin40 (Cx40; A96S, M163V, and G38D), the primary component of the atrial gap junction channel, are associated with atrial fibrillation and retain the ability to form functional channels. We determined the biophysical properties of these mutant gap junctions in transiently transfected HeLa and N2A cells. All three mutants showed macroscopic junctional conductances over the range of 0.5 to 40 nS, and voltage dependences comparable to those of wild-type (WT) Cx40. However, the unitary conductance of G38D channels was ~1.6-fold higher than that of WT Cx40 channels (~220 vs. ~135 pS), whereas the unitary conductances of the A96S and M163V mutants were similar to that of WT Cx40. Furthermore, the M163V and G38D channels exhibited approximately two- and approximately fivefold higher permeability to the anionic dye Lucifer yellow (LY) relative to K+ (LY/K+) compared with that of WT Cx40, whereas A96S LY transfer was similar to that of WT (G38D > M163V > A96S ? Cx40WT). In contrast, G38D channels were almost impermeable to cationic ethidium bromide (EtBr), suggesting that G38D alters channel selectivity. Conversely, A96S and M163V channels showed enhanced EtBr permeability relative to WT Cx40, with the following permeability order: M163V > A96S > Cx40WT > G38D. Altered conductive and permeability properties of mutant channels suggest an essential role for Cx40-mediated biochemical and electrical coupling in cardiac tissues. The altered properties of the three single-base substitution mutants may play a role in mechanisms of reentry arrhythmias. © 2015 Santa Cruz et al. | URI: | https://doi.org/10.1085/jgp.201511475 https://hdl.handle.net/11147/10241 |
ISSN: | 0022-1295 |
Appears in Collections: | Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection |
Files in This Item:
File | Size | Format | |
---|---|---|---|
jgp_201511475.pdf | 2.07 MB | Adobe PDF | View/Open |
CORE Recommender
SCOPUSTM
Citations
21
checked on Nov 9, 2024
WEB OF SCIENCETM
Citations
19
checked on Oct 26, 2024
Page view(s)
624
checked on Nov 11, 2024
Download(s)
66
checked on Nov 11, 2024
Google ScholarTM
Check
Altmetric
Items in GCRIS Repository are protected by copyright, with all rights reserved, unless otherwise indicated.