Antisense oligodeoxynucleotides (AS-oligos) targeted to the Na+/Ca2+exchanger (NCX) inhibit NCX-mediated Ca2+ influx in mesenteric artery (MA) myocytes [ Am. J. Physiol.269 ( Cell Physiol. 38): C1340-C1345, 1995]. Here, we show AS-oligo knockdown of NCX-mediated Ca2+ efflux. In initial experiments, the cytosolic free Ca2+ concentration ([Ca2+]cyt) was raised, and sarcoplasmic reticulum (SR) Ca2...

Besides the sarcoplasmic reticulum (SR) Ca 2 -ATPase (SERCA), the sarcolemmal Na –Ca exchanger (NCX) is the most important Ca transport protein responsible for maintaining the Ca balance of the myocyte. It catalyzes the transport of Ca across the membrane in exchange for Na in a reversible manner. Its activity is called “forward” when Na is transported inward and Ca outward and “reversed” when ...

Here, we describe the improved antiarthritic properties of a nitric oxide-releasing derivative of prednisolone that includes a sparing of the effects on bone. Glucocorticoids are widely used in the treatment of chronic inflammatory pathologies, but their use is often accompanied by side effects, including osteoporosis. Recently, a new steroid able to release low levels of nitric oxide showed po...

AIMS Andersen-Tawil syndrome (ATS1)-associated ventricular arrhythmias are initiated by premature ventricular activity (PVA) resulting from diastolic Ca(2+) (Ca(D)) accumulation. We hypothesized that relatively high Na(+)-Ca(2+) exchanger (NCX) expression coupled with slower Ca(2+) uptake may constitute an arrhythmogenic substrate during drug-induced ATS1 (DI-ATS1). METHODS AND RESULTS DI-ATS...

Increased Na+-Ca2+ exchange (NCX) activity in heart failure and hypertrophy may compensate for depressed sarcoplasmic reticular Ca2+ uptake, provide inotropic support through reverse-mode Ca2+ entry, and/or deplete intracellular Ca2+ stores. NCX is electrogenic and depends on Na+ and Ca2+ transmembrane gradients, making it difficult to predict its effect on the action potential (AP). Here, we e...

BACKGROUND The Na(+)/Ca(2+) exchanger (NCX) has been implied to cause arrhythmias. To date, information on the role of NCX in arrhythmogenesis derived from models with increased NCX expression, hypertrophy, and heart failure. Furthermore, the exact mechanism by which NCX exerts its potentially proarrhythmic effect, ie, by promoting early afterdepolarization (EAD) or delayed afterdepolarization ...

The effects of a nitric oxide (NO)-releasing derivative of aspirin, NCX-4016, on gastric functional and ulcerogenic responses in rat stomachs were examined in comparison with those of aspirin. Topical application of aspirin (80 mM) to the stomach markedly decreased transmucosal potential difference and slightly increased luminal pH (acid back-diffusion) with minimal effect on mucosal blood flow...

The sodium-calcium exchange (NCX) plays a pivotal role in regulating contractility and electrical activity in the heart. However, the effects of NCX blockers on ventricular arrhythmias are still controversial. We examined the effects of KB-R7943 (KBR) and SEA0400 (SEA), two NCX blockers, on aconitine-induced arrhythmias in guinea pigs using the ECG recordings and the current-clamp method. Using...

Heart failure (HF) is a significant problem, affecting more than 2 million people in the United States alone.1 When severe, it is associated with a 50% 2-year mortality rate attributable to either contractile dysfunction or sudden death from ventricular tachycardia and ventricular fibrillation.1 The underlying molecular mechanisms have not yet been defined, but there is considerable evidence fr...

Heart failure (HF) is a significant problem, affecting more than 2 million people in the United States alone.1 When severe, it is associated with a 50% 2-year mortality rate attributable to either contractile dysfunction or sudden death from ventricular tachycardia and ventricular fibrillation.1 The underlying molecular mechanisms have not yet been defined, but there is considerable evidence fr...