The Na(+)-Ca(2+) exchanger (NCX) is involved in regulation of intracellular Ca(2+) concentration. A specific inhibitor of NCX has been required for clarification of the physiological and pathological roles of NCX. We have developed 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline (SEA0400), a highly potent and selective inhibitor of NCX. SEA0400 in the concentration range that inhibit...

BACKGROUND Reduced myocardial contractility is often attributed to altered Ca(2+) transients and expression of Ca(2+)-ATPase of the SR (SERCA) and Na+/Ca(2+)exchanger (NCX) genes. AIMS To assess myocardial expression of SERCA and NCX protein levels in left ventricular (LV) remodelling due to chronic severe mitral regurgitation (MR). METHODS Myocardial expression of SERCA/NCX in biopsy speci...

The Na⁺/Ca²⁺ exchanger (NCX) is an important electrogenic transporter in maintaining Na⁺ and Ca²⁺ homeostasis in a variety of mammalian organs, and is involved in the physiological and pathophysiological regulation of Ca²⁺ concentration in the myocardium. It can affect cardial structure, electrophysiology and contractile properties. The role of the NCX in heart cells following ischemia/reperfus...

This study investigated the role of the Na+/Ca2+ exchanger (NCX) in regulating cytosolic intracellular Ca2+ concentration ([Ca2+]i) during anoxia/reoxygenation in guinea pig ventricular myocytes. The hypothesis that the NCX is the predominant mechanism mediating [Ca2+]i overload in this model was tested through inhibition of NCX expression by an antisense oligonucleotide. Immunocytochemistry re...

We examined the effects of SEA0400 and CGP-37157 on the plasmalemmal Na(+)-Ca(2+) exchanger (NCX) and mitochondrial NCX using H9c2 cardiomyocytes loaded with Ca(2+)-sensitive fluorescent probes. The plasmalemmal NCX activity, which was measured as the increase in cytoplasmic Ca(2+) concentration after application of low Na(+) extracellular solution, was inhibited by SEA0400 but not by CGP-37157...

BACKGROUND The aim of this study was to examine potential therapeutic effect of the two NO donors NCX 2057 (3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid) 4-(nitrooxy)butyl ester) and SNP (sodium nitroprusside) on the early allergic airway response in the peripheral lung. METHODS The experiments were performed in guinea pig lung parenchyma (GPLP) derived from ovalbumin (OVA) sensitized guine...

Liu, Li, Yukisato Ishida, Gbolahan Okunade, Gary E. Shull, and Richard J. Paul. Role of plasma membrane Ca -ATPase in contraction-relaxation processes of the bladder: evidence from PMCA geneablated mice. Am J Physiol Cell Physiol 290: C1239–C1247, 2006. First published November 16, 2005; doi:10.1152/ajpcell.00440.2005.—We investigated the roles and relationships of plasma membrane Ca ATPase (PM...

Overexpression of calsequestrin (CSQ) induces severe cardiac hypertrophy, whereas overexpression of Na(+)-Ca(2+) exchanger (NCX) does not affect cardiac weight. To investigate a possible beneficial effect of NCX in hypertrophy, we produced transgenic mice overexpressing both NCX and CSQ (NCX/CSQ). Surprisingly, these mice developed severe heart failure. The heart/body weight ratio was enhanced ...

The Na(+)-Ca(2+) exchanger (NCX) is one of the essential regulators of Ca(2+) homeostasis in cardiomyocytes and thus an important modulator of the cardiac contractile function. The purpose of this review is to survey recent advances in cardiac NCX research, with particular emphasis on molecular and pharmacological aspects. The NCX function is thought to be regulated by a variety of cellular fac...

The sodium/calcium exchanger (NCX) is a widespread transporter that exchanges sodium and calcium ions across excitable membranes. Normally, NCX mainly operates in its "forward" mode, harnessing the electrochemical gradient of sodium ions to expel calcium. During membrane depolarization or elevated internal sodium levels, NCX can instead switch the direction of net flux to expel sodium and allow...