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Enhanced sarcoplasmic reticulum Ca2+ leak and increased Na+-Ca2+ exchanger function underlie delayed afterdepolarizations in patients with chronic atrial fibrillation

Background: Delayed afterdepolarizations (DADs) carried by Na+-Ca2+-exchange current (INCX) in response to sarcoplasmic reticulum (SR) Ca2+ leak can promote atrial fibrillation (AF). The mechanisms leading to delayed afterdepolarizations in AF patients have not been defined. Methods and Results: Pro...

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Main Authors: Voigt, Niels (Author) , Sun, Qiang (Author) , Wieland, Thomas (Author) , Dobrev, Dobromir (Author)
Format: Article (Journal)
Language:English
Published: May 1, 2012
In: Circulation
Year: 2012, Volume: 125, Issue: 17, Pages: 2059-2070
ISSN:1524-4539
DOI:10.1161/CIRCULATIONAHA.111.067306
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1161/CIRCULATIONAHA.111.067306
Verlag, kostenfrei, Volltext: https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.111.067306
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Author Notes:Niels Voigt, MD, Na Li, PhD, Qiongling Wang, PhD, Wei Wang, PhD, Andrew W. Trafford, PhD, Issam Abu-Taha, BSc, Qiang Sun, PhD, Thomas Wieland, PhD, Ursula Ravens, MD, Stanley Nattel, Md, Xander H.T. Wehrens, MD, PhD, Dobromir Dobrev, MD
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Summary:Background: Delayed afterdepolarizations (DADs) carried by Na+-Ca2+-exchange current (INCX) in response to sarcoplasmic reticulum (SR) Ca2+ leak can promote atrial fibrillation (AF). The mechanisms leading to delayed afterdepolarizations in AF patients have not been defined. Methods and Results: Protein levels (Western blot), membrane currents and action potentials (patch clamp), and [Ca2+]i (Fluo-3) were measured in right atrial samples from 76 sinus rhythm (control) and 72 chronic AF (cAF) patients. Diastolic [Ca2+]i and SR Ca2+ content (integrated INCX during caffeine-induced Ca2+ transient) were unchanged, whereas diastolic SR Ca2+ leak, estimated by blocking ryanodine receptors (RyR2) with tetracaine, was ≈50% higher in cAF versus control. Single-channel recordings from atrial RyR2 reconstituted into lipid bilayers revealed enhanced open probability in cAF samples, providing a molecular basis for increased SR Ca2+ leak. Calmodulin expression (60%), Ca2+/calmodulin-dependent protein kinase-II (CaMKII) a...
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Originally published 28 Mar 2012
Gesehen am 05.10.2018
Physical Description:Online Resource
ISSN:1524-4539
DOI:10.1161/CIRCULATIONAHA.111.067306

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