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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| Hauptverfasser: | , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
May 1, 2012
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| In: |
Circulation
Year: 2012, Jahrgang: 125, Heft: 17, Pages: 2059-2070 |
| ISSN: | 1524-4539 |
| DOI: | 10.1161/CIRCULATIONAHA.111.067306 |
| Online-Zugang: | 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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| Verfasserangaben: | 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 |
MARC
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| 245 | 1 | 0 | |a Enhanced sarcoplasmic reticulum Ca2+ leak and increased Na+-Ca2+ exchanger function underlie delayed afterdepolarizations in patients with chronic atrial fibrillation |c 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 |
| 246 | 3 | 3 | |a Enhanced sarcoplasmic reticulum Ca2 plus leak and increased Na plus-Ca2 plus exchanger function underlie delayed afterdepolarizations in patients with chronic atrial fibrillation |
| 246 | 3 | 3 | |a Enhanced sarcoplasmic reticulum Ca2+ leak and increased Na +-Ca2 + exchanger function underlie delayed afterdepolarizations in patients with chronic atrial fibrillation |
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| 520 | |a 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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