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
Issue Date: 2015
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/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 SizeFormat 
jgp_201511475.pdf2.07 MBAdobe PDFView/Open
Show full item record



CORE Recommender

SCOPUSTM   
Citations

18
checked on Feb 16, 2024

WEB OF SCIENCETM
Citations

16
checked on Jan 27, 2024

Page view(s)

504
checked on Feb 26, 2024

Download(s)

18
checked on Feb 26, 2024

Google ScholarTM

Check




Altmetric


Items in GCRIS Repository are protected by copyright, with all rights reserved, unless otherwise indicated.