Na(+)/Ca(2+) exchanger (NCX) proteins extrude Ca(2+) from the cell to maintain cellular homeostasis. Since NCX proteins contribute to numerous physiological and pathophysiological events, their pharmacological targeting has been desired for a long time. This intervention remains challenging owing to our poor understanding of the underlying structure-dynamic mechanisms. Recent structural studies...

With the help of single-cell microflorimetry, Ca radiotracer fluxes, and patch-clamp in whole-cell configuration, we examined the effect of the amiloride derivative 3-amino-6-chloro-5[(4-chloro-benzyl)amino]-N-[[(2,4-dimethylbenzyl)amino]iminomethyl]-pyrazinecarboxamide (CB-DMB) on the activity of the three isoforms of the Na /Ca exchanger (NCX) and on several other membrane currents including ...

OBJECTIVE There is recent evidence that Ca(2+) influx via reverse mode Na(+)/Ca(2+) exchange (NCX) at the time of reperfusion can contribute to cardiomyocyte hypercontracture. However, forward NCX is essential for normalization of [Ca(2+)](i) during reperfusion, and its inhibition may be detrimental. This study investigates the effect of NCX inhibition with KB-R7943 at the time of reperfusion o...

We examined the possible role of the Na-Ca exchange (NCX) in the arrhythmogenesis in rat atrial preparations applying microelectrode technique. In control Tyrode solution preparations isolated from the sinoatrial area contracted with frequency of 48+/-4 min(-1) (group I) or 84+/-7 min(-1) (group II). In preparation beating with low frequency partial inhibition of NCX by administration of Ni2+ (...

The widely accepted model to explain the positive inotropic effect of cardiac glycosides invokes altered Na+-Ca2+ exchange activity secondary to Na+ pump inhibition. However, proof of this model is lacking and alternative mechanisms have been proposed. We directly tested the role of the Na+-Ca2+ exchanger in the action of the glycoside ouabain using Na+-Ca2+ exchanger knockout mice. Ablation of...

AIMS This study was designed to evaluate the effects of the Na(+)/Ca(2+) exchange (NCX) inhibitor SEA0400 on Ca(2+) handling in isolated canine ventricular myocytes. METHODS AND RESULTS Intracellular Ca(2+) ([Ca(2+)](i)) transients, induced by either field stimulation or caffeine flush, were monitored using Ca(2+) indicator dyes. [Ca(2+)](i)-dependent modulation of the inhibitory effect of SE...

Liu, Jing, Kenneth W. L. Kam, Gudrun H. Borchert, Gennadi M. Kravtsov, Heather J. Ballard, and Tak Ming Wong. Further study on the role of HSP70 on Ca homeostasis in rat ventricular myocytes subjected to simulated ischemia. Am J Physiol Cell Physiol 290: C583–C591, 2006. First published October 5, 2005; doi:10.1152/ajpcell.00145.2005.—We hypothesized that activation of heat shock protein 70 (HS...

The Na(+)/Ca(2+) exchanger (NCX) is a bidirectional transporter that is controlled by membrane potential and transmembrane gradients of Na(+) and Ca(2+). Although two isoforms of NCX1 and NCX2 are coexpressed on the basolateral membrane of the distal nephron, the functional significance of these isoforms is not entirely clear. Therefore, we used NCX1- and NCX2-heterozygote knockout mice (KO) an...

Endothelial nitric oxide (NO) synthase (eNOS) is controlled by Ca(2+)/calmodulin and caveolin-1 in caveolae. It has been recently suggested that Na(+)/Ca(2+) exchanger (NCX), also expressed in endothelial caveolae, is involved in eNOS activation. To investigate the role played by NCX in NO synthesis, we assessed the effects of Na(+) loading (induced by monensin) on rat aortic rings and cultured...

We investigated the roles of three regulatory proteins that impact [Ca 2+ ]i within cardiac myocytes of Drosophila melanogaster. The NCX (Na + /Ca 2+ exchanger), PMCA (plasma membrane Ca 2+ -ATPase) and SERCA (sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase) were compromised by ionic, pharmacological, mutationalmanipulation, and with a combination of approaches, while heart rate (HR) was monit...