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A trial fibrillation (AF), the most common human cardiac arrhythmia, is associated with abnormal intracellular Ca2+ handling. Diastolic Ca2+ release from the sarcoplasmic reticulum via "leaky" ryanodine receptors (RyR2s) is hypothesized to contribute to arrhythmogenesis in AF, but the molecular mechanisms are incompletely understood. Here, we have shown(More)
Triadin 1 is a major transmembrane protein in cardiac junctional sarcoplasmic reticulum (SR), which forms a quaternary complex with the ryanodine receptor (Ca(2+) release channel), junctin, and calsequestrin. To better understand the role of triadin 1 in excitation-contraction coupling in the heart, we generated transgenic mice with targeted overexpression(More)
The contractile response and myocardial content of Gi-proteins were examined in cardiac preparations from explanted hearts of four different patients with end-stage heart failure. Three patients had idiopathic dilated cardiomyopathy and one patient had inflammatory heart disease. Preparations from patients with idiopathic dilated cardiomyopathy showed(More)
OBJECTIVE The natriuretic peptides (NPs), atrial (ANP), B-type (BNP), and C-type (CNP) natriuretic peptides as well as their respective receptor-guanylyl cyclases (GC-A for ANP and BNP, and GC-B for CNP) are expressed in the heart. However, the local role of NPs in the regulation of cardiac contractility and the mutual interactions of NPs remain(More)
Adenosine added to isolated electrically driven preparations of human ventricular heart muscle antagonized the positive inotropic effect of isoprenaline (mean EC50 19 mumol 1(-1), n = 9). Similar effects were observed with the adenosine receptor agonist (-)-N6-phenylisopropyladenosine (mean EC50 0.5 mumol 1(-1), n = 7). These data provide functional(More)
Type 1 phosphatase activity was increased in membrane vesicles from failing human ventricles compared with non-failing controls. Likewise, expression of the mRNA encoding for type 1 phosphatase was enhanced by 37%. The present study provides evidence that alterations of phosphatase activity coincide with end-stage heart failure. Thus, enhanced activity of(More)
Chronic β-adrenoceptor stimulation leads to desensitization of the myocardial adenylyl cyclase signalling pathway which includes β-adrenoceptor downregulation and upregulation of Gi-protein α-subunits. However, these investigations have mainly been done in cellular preparations. In this study we report that isoprenaline infusion in vivo leads to an increase(More)
Okadaic acid exerts a positive inotropic effect in cardiac preparations. We studied whether the positive inotropic effect of okadaic acid in cardiac preparations could be due to phosphatase inhibition and whether this inhibition affects the phosphorylation of cardiac proteins. In papillary muscles from guinea pigs, 30 microM okadaic acid increased force of(More)
OBJECTIVE An increased expression of adenosine receptors is a promising target for gene therapy aimed at protecting the myocardium against ischemic damage, but may alter cardiac electrophysiology. We therefore studied the effects of heart-directed overexpression of A(3) adenosine receptors (A(3)ARs) at different gene doses on sinus and atrio-ventricular(More)
Reversible protein phosphorylation is an essential regulatory mechanism in many cellular functions. In contrast to protein kinases, the role and regulation of protein phosphatases has remained ambiguous. To address this issue, we generated transgenic mice that overexpress the catalytic subunit alpha of protein phosphatase 2A (PP2A) (PP2Acalpha) in the heart(More)