Levosimendan, a known calcium sensitizer with positive inotropic and vasodilating properties, might also be cardioprotective during ischemia-reperfusion (I/R) insult. Its effects on calcium homeostasis and apoptosis in I/R injury remain unclear. Na(+)/Ca(2+) exchanger (NCX) is a critical mediator of calcium homeostasis in cardiomyocytes, with reverse-mode NCX activity responsible for intracellu...

BACKGROUND In neonatal heart, plasma membrane Na+-Ca2+ exchange (NCX) and Ca2+ influx channels play greater roles in intracellular Ca2+ concentration [Ca2+]i regulation compared with the sarcoplasmic reticulum (SR). In neonatal (aged 0-3 days) and adult (aged 84 days) rat cardiac myocytes, we determined the mechanisms underlying greater sensitivity of the neonatal myocardium to inhibition by vo...

To investigate the effect of extracellular pH on endothelial nitric oxide synthase (eNOS) in human pulmonary arteries, we measured eNOS activity and expression as well as some ion channels in human pulmonary arterial endothelial cells (HPAEC) exposed to various pH levels (6.6-8.0). eNOS activity was found to increase with alkalization and decrease with acidification, while Ca2+ uptake into HPAE...

In brain ischemia, gating of postsynaptic glutamate receptors and other membrane channels triggers intracellular Ca2+ overload and cell death. In excitotoxic settings, the initial Ca2+ influx through glutamate receptors is followed by a second uncontrolled Ca2+ increase that leads to neuronal demise. Here we report that the major plasma membrane Ca2+ extruding system, the Na+/Ca2+ exchanger (NC...

Using a theoretical model of smooth muscle cell from rat mesenteric arterioles, we investigated calcium dynamics in normal and hypertensive vascular wall. The model incorporated a detailed description of plasma membrane, cytosol and intracellular stores. Inhibition of Na + -K + pump (NaK) simulated the effect of ouabain in salt sensitive hypertension. The inhibition caused intracellular sodium ...

Introduction Cytosolic Ca2+ regulates several cellular processes and its concentration is, in turn, finely regulated by various channels, pumps and exchangers. The Na/Ca exchanger (NCX) and the plasma membrane Ca2+-ATPase (PMCA) pump are two concurrent mechanisms for Ca2+ extrusion from the cell (Carafoli, 1994; Blaustein & Lederer, 1999; Philipson & Nicoll, 2000; Strehler & Treiman, 2004; Pras...

The involvement of Ca2+ entry via the Na+/Ca2+ exchanger (NCX) in myogenic constriction of rat posterior cerebral arteries was investigated. RT-PCR identified mRNA for NCX1, 2, and 3 in the arteries. Na+ removal increased [Ca2+]i, which was reduced by the NCX inhibitor SEA0400. SEA0400 inhibited the development, but not the steady-state, of pressure-induced myogenic constriction, whereas it dec...

In addition to inhibiting cyclooxygenase (COX)-1-derived prostanoid biosynthesis, aspirin acetylates COX-2, enabling the conversion of arachidonic acid to 15(R)-epi lipoxin A4, or aspirin-triggered lipoxin (ATL). Selective COX-2 inhibitors block ATL formation and exacerbate mucosal injury in rats treated with aspirin. In the present study, we have examined whether inhibition of COX-2 activity i...

Background and Purpose—A prominent feature of cerebral ischemia is the excessive intracellular accumulation of both Na and Ca ions, which results in subsequent cell death. The plasma membrane Na /Ca exchanger (NCX), regulates the distribution of these ions acting either in the forward mode or in its reverse mode and it can play a critical role in brain ischemia. However, it is unclear whether t...

Ovarian cancer is a gynecological malignancy that is commonly treated by cytoreductive surgery followed by cisplatin treatment. However, the cisplatin treatment, although successful initially, is not effective in the treatment of the recurrent disease that invariably surfaces within a few months of the initial treatment. The refractory behavior is attributed to the increased levels of cellular ...