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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(More)
BACKGROUND Congestive heart failure (CHF) is a common cause of atrial fibrillation. Focal sources of unknown mechanism have been described in CHF-related atrial fibrillation. The authors hypothesized that abnormal calcium (Ca(2+)) handling contributes to the CHF-related atrial arrhythmogenic substrate. METHODS AND RESULTS CHF was induced in dogs by(More)
2؉ transport in remodeled human atrium, but appropriate models are limited. Objective: To study AF, we developed a new human atrial action potential (AP) model, derived from atrial experimental results and our human ventricular myocyte model. to mimic Kv1.5 loss-of-function increased [Ca 2؉ ] i and caused early afterdepolarizations under adrenergic stress,(More)
BACKGROUND The ultrarapid outward current I(Kur) is a major repolarizing current in human atrium and a potential target for treating atrial arrhythmias. The effects of selective block of I(Kur) by low concentrations of 4-aminopyridine or the biphenyl derivative AVE 0118 were investigated on right atrial action potentials (APs) in trabeculae from patients in(More)
BACKGROUND Clinical and experimental evidence suggest that the parasympathetic nervous system is involved in the pathogenesis of atrial fibrillation (AF). However, it is unclear whether changes in G-protein-coupled inward rectifying K(+) current (I(K,ACh)) contribute to chronic AF. METHODS AND RESULTS In the present study, we used electrophysiological(More)
BACKGROUND Ca2+ leak from the sarcoplasmic reticulum (SR) may play an important role in triggering and/or maintaining atrial arrhythmias, including atrial fibrillation (AF). Protein kinase A (PKA) hyperphosphorylation of the cardiac ryanodine receptor (RyR2) resulting in dissociation of the channel-stabilizing subunit calstabin2 (FK506-binding protein or(More)
Inadequacies in current therapies for atrial fibrillation have made new drug development crucial. Conventional antiarrhythmic drugs increase the risk of ventricular proarrhythmia. In drug development, the focus has been on favourable multichannel-blocking profiles, atrial-specific ion-channels, and novel non-channel targets (upstream therapy). Molecular(More)
1. The putative inhibitory effects of verapamil and diltiazem on neuronal non-L-type Ca2+ channels were studied by investigating their effects on either K+- or veratridine-evoked [3H]-dopamine ([3H]-DA) release in rat striatal slices. Involvement of N-, P- and Q-type channels was identified by sensitivity of [3H]-DA release to omega-conotoxin GVIA(More)
Cardiac ryanodine receptor type 2 plays a key role in excitation-contraction coupling. The ryanodine receptor type 2 channel protein is modulated by various post-translational modifications, including phosphorylation by protein kinase A and Ca(2+)/calmodulin protein kinase II. Despite extensive research in this area, the functional effects of ryanodine(More)