© 2001 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
How can overexpression of Na+,Ca2+-exchanger compensate the negative inotropic effects of downregulated SERCA?
Department of Physiology, Martin-Luther-University, Halle, Germany
* Tel.: +49-345-557-1886; fax: +49-345-557-4019 gerrit.isenberg@medizin.uni-halle.de
Received 1 November 2000; accepted 1 November 2000
| The first 150 words of the full text of this article appear below. |
See article by Terracciano et al. [2] (pages 38–47) in this issue.
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1 Importance of the Na+/Ca2+-exchanger for the Ca2+ distribution in the failing human heart |
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The failing human ventricle suffers from two major problems: (1) During diastole, relaxation is retarded and remains eventually incomplete. (2) During systole, the force-frequency relation is blunted, i.e. an increase from 60 to 120 beats-per-min does not increase the contractile force as it is typical in non-failing tissue. Both problems have been linked to reduced expression and function of sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA) proteins. Studies in isolated human ventricular trabeculae [1] have shown that incomplete Ca2+ reuptake by SERCA can cause (1) a diastolic accumulation of Ca2+ ions in the cytosol which impairs diastolic relaxation, and (2) a reduction of releasable SR Ca2+ with the consequence of a reduced systolic Ca2+ activation of force and a blunted force-frequency relation. Since failing human myocardium was shown to overexpress the Na+/Ca2+-exchanger (mRNA and protein [1]),
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2 Transgenic mice with overexpressed Na+/Ca2+-exchanger as a model |
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3 The balance of Ca2+ fluxes |
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4 Na+/Ca2+-exchange provides both Ca2+ efflux and Ca2+ influx |
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5 The Ca2+ transients in myocytes from transgenic mice |
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6 In myocytes from transgenic mice, SR Ca2+ load is augmented |
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7 Problems in quantification of the Ca2+ flux |
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8 Mechanisms by which overexpressed Na+/Ca2+-exchanger could augment SR Ca2+ filling |
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8.1 Faster decay of [Ca2+]c
8.2 Faster accumulation of [Na+]SL
8.3 Longer action potential (AP)
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9 The overexpressed Na+/Ca2+-exchanger can compensate for suppressed SERCA activity |
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10 From the transgenic mice back to the failing human heart |
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