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

• Verfasst von: Voigt, Niels [VerfasserIn]
• Verfasst von: Sun, Qiang [VerfasserIn]
• Verfasst von: Wieland, Thomas [VerfasserIn]
• Verfasst von: Dobrev, Dobromir [VerfasserIn]
• Titel: Enhanced sarcoplasmic reticulum Ca2+ leak and increased Na+-Ca2+ exchanger function underlie delayed afterdepolarizations in patients with chronic atrial fibrillation
• Verf.angabe: 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
• E-Jahr: 2012
• Jahr: May 1, 2012
• Umfang: 12 S.
• Fussnoten: Plus-Zeichen sind im Titel hochgestellt ; Originally published 28 Mar 2012 ; Gesehen am 05.10.2018
• Titel Quelle: Enthalten in: Circulation
• Ort Quelle: Philadelphia, Pa. : Lippincott, Williams & Wilkins, 1950
• Jahr Quelle: 2012
• Band/Heft Quelle: 125(2012), 17, Seite 2059-2070
• ISSN Quelle: 1524-4539
• DOI: doi:10.1161/CIRCULATIONAHA.111.067306
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1581579594

Abstract

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...