Enhanced Sarcoplasmic Reticulum Ca-leak and Increased Na-Ca- Exchanger Function Underlie Delayed Afterdepolarizations in Patients with Chronic Atrial Fibrillation
نویسندگان
چکیده
Division of Experimental Cardiology, Dept of Experimental & Clinical Pharmacology, Medical Faculty Mannheim, University of Heidelberg, Mannheim; Dept of Pharmacology & Toxicology, Dresden University of Technology, Dresden, Germany; Dept of Molecular Physiology & Biophysics, Dept of Medicine, Baylor College of Medicine, Houston, TX; Unit of Cardiac Physiology, Manchester Academic Health Sciences Centre, Manchester, United Kingdom; Dept of Medicine, Montreal Heart Institute & Université de Montréal, Montreal, Canada
منابع مشابه
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(+)-Ca(2+)-exchange current (I(NCX)) in response to sarcoplasmic reticulum (SR) Ca(2+) 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 [C...
متن کاملArrhythmia/Electrophysiology Enhanced Sarcoplasmic Reticulum Ca Leak and Increased Na -Ca Exchanger Function Underlie Delayed Afterdepolarizations in Patients With Chronic Atrial Fibrillation
constitutively phosphorylated RyR2 at Ser2814 showed a higher incidence of Ca sparks and increased susceptibility to pacing-induced AF compared with controls. The relationship between [Ca ]i and INCX density revealed INCX upregulation in cAF. Spontaneous Ca release events accompanied by inward INCX currents and delayed afterdepolarizations/triggered activity occurred more often and the sensitiv...
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RATIONALE Abnormal calcium release from sarcoplasmic reticulum (SR) is considered an important trigger of atrial fibrillation (AF). Whereas increased Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity has been proposed to contribute to SR leak and AF induction, downstream targets of CaMKII remain controversial. OBJECTIVE To test the hypothesis that inhibition of CaMKII-phosphoryl...
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BACKGROUND Atrial fibrillation (AF) risk has been associated with leaky ryanodine receptor 2 (RyR2) Ca release channels. Patients with mutations in RyR2 or in the sarcoplasmic reticulum Ca-binding protein calsequestrin 2 (Casq2) display an increased risk for AF. Here, we examine the underlying mechanisms of AF associated with loss of Casq2 and test mechanism-based drug therapy. METHODS AND RE...
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OBJECTIVE Although AF-induced atrial contractile dysfunction has significant clinical implications the underlying intracellular mechanisms are poorly understood. METHODS From the right atrial appendages of 59 consecutive patients undergoing mitral valve surgery (31 in SR, 28 in chronic AF) thin muscle preparations (diameter<0.7 mm) were isolated. Isometric force of contraction was measured in...
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