Show simple item record

dc.contributor.authorCruz, A.S.
dc.contributor.authorMeşe, G.
dc.contributor.authorValiuniene, L.
dc.contributor.authorBrink, P.R.
dc.contributor.authorWhite, T.W.
dc.contributor.authorValiunas, V.
dc.descriptionPubMed: 26503720en_US
dc.description.abstractGap 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.en_US
dc.description.sponsorshipNational Institutes of Health: GM88180, AR59505, GM088181en_US
dc.description.sponsorshipThis work was supported by the National Institutes of Health (grants GM088181 to V. Valiunas, GM88180 to P.R. Brink, and AR59505 to T.W. White). The authors declare no competing financial interests.en_US
dc.publisherRockefeller University Pressen_US
dc.titleAltered conductance and permeability of Cx40 mutations associated with atrial fibrillationen_US
dc.relation.journalJournal of General Physiologyen_US
dc.contributor.departmentIzmir Isntitute of Technologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US

Files in this item


There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record