Inhibition of the sodium-calcium exchanger via SEA0400 altered manganese-induced T(1) changes in isolated perfused rat hearts.
Summary of "Inhibition of the sodium-calcium exchanger via SEA0400 altered manganese-induced T(1) changes in isolated perfused rat hearts."
Manganese (Mn(2+) )-enhanced MRI (MEMRI) provides the potential for the in vivo evaluation of calcium (Ca(2+) ) uptake in the heart. Recent studies have also suggested the role of the sodium-calcium (Na(+) -Ca(2+) ) exchanger (NCX) in Mn(2+) retention, which may have an impact on MEMRI signals. In this study, we investigated whether MEMRI with fast T(1) mapping allowed the sensitive detection of changes in NCX activity. We quantified the dynamics of the Mn(2+) -induced T(1) changes in isolated perfused rat hearts in response to SEA0400, an NCX inhibitor. The experimental protocol comprised 30 min of Mn(2+) perfusion (wash-in), followed by a 30-min wash-out period. There were three experimental groups: 1, NCX inhibition by 1 µ m SEA0400 during Mn(2+) wash-in only (SEAin, n = 6); 2, NCX inhibition by 1 µ m SEA0400 during Mn(2+) wash-out only (SEAout, n = 6); 3, no NCX inhibition during both wash-in and wash-out to serve as the control group (CNTL, n = 5). Rapid T(1) mapping at a temporal resolution of 3 min was performed throughout the perfusion protocol using a triggered saturation-recovery Look-Locker sequence. Our results showed that NCX inhibition during Mn(2+) wash-in caused a significant increase in relaxation rate (R(1) ) at the end of Mn(2+) perfusion. During the wash-out period, NCX inhibition led to less reduction in R(1) . Further analysis of Mn(2+) content in myocardium with flame atomic absorption spectroscopy was consistent with the MRI findings. These results suggest that Mn(2+) accumulation and retention in rat hearts are, in part, dependent on NCX activity. Hence, MEMRI may provide an imaging method that is also sensitive to changes in NCX activity. Copyright © 2012 John Wiley & Sons, Ltd.
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA; Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH, USA.
This article was published in the following journal.
Name: NMR in biomedicine
Medical and Biotech [MESH] Definitions
An electrogenic ion exchange protein that maintains a steady level of calcium by removing an amount of calcium equal to that which enters the cells. It is widely distributed in most excitable membranes, including the brain and heart.
Manganese poisoning is associated with chronic inhalation of manganese particles by individuals who work with manganese ore. Clinical features include CONFUSION; HALLUCINATIONS; and an extrapyramidal syndrome (PARKINSON DISEASE, SECONDARY) that includes rigidity; DYSTONIA; retropulsion; and TREMOR. (Adams, Principles of Neurology, 6th ed, p1213)
Inorganic chemicals that contain manganese as an integral part of the molecule.
Sodium Channel Blockers
A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.
Calcium Channel Blockers
A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms.
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