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Reverses Remodeling der intrazellulären Ca2+-Homöostase: Neue Konzepte zur Pathophysiologie und Therapie der Herzinsuffizienz

Reverse Remodeling of the intracellular Ca2+-homeostasis: New concepts of pathophysiology and therapy of heart failure

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Summary

Cardiac contraction is dependent on a rapid alteration of the intracellular Ca2+ concentration, especially the Ca2+ released during systole. In end-stage heart failure, cardiac contractility is depressed due to alterations in the structure and function of proteins or protein complexes. Over recent years, new insights have been obtained regarding the regulation of the intracellular Ca2+ homeostasis and its pathophysiological alteration in end-stage heart failure. This review focuses on the mechanisms involved in the release of Ca2+ from the sarcoplasmic reticulum (SR) during systole via the ryanodine receptors and the Ca2+-uptake into the SR by the sarcoplasmic reticulum Ca2+-ATPase (SERCA 2a). In addition, new therapeutic options will be introduced which may be of importance for the treatment of heart failure patients.

Zusammenfassung

Die Funktion der Herzmuskelzelle beruht auf einem schnellen Wechsel der intrazellulären Ca2+-Konzentration und ist dabei wesentlich von der während der Systole in das Zytoplasma freigesetzten Ca2+-Konzentration abhängig. Bei der Herzinsuffizienz ist die kardiale Kontraktilität durch Veränderungen in der Struktur und Funktion von Proteinen/Proteinkomplexen gestört. In den letzten Jahren wurden neue Erkenntnisse im Hinblick auf die Regulation der intrazellulären Ca2+-Homöostase und ihre pathophysiologischen Veränderungen im Endstadium der Herzinsuffizienz gewonnen, die für die Therapie der Herzinsuffizienz von Bedeutung sind. Dies betrifft insbesondere die Vorgänge der Ca2+-Freisetzung aus dem sarkoplasmatischen Retikulum (SR) über die Ryanodin-Rezeptoren sowie die Ca2+-Aufnahme in das SR durch die sarkoplasmatische Ca2+-ATPase (SERCA 2a). Der vorliegende Artikel fasst aktuelle Forschungsergebnisse zusammen und zeigt neue Therapieoptionen auf, die sich hieraus ergeben können.

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Authors and Affiliations

  1. Labor für Herzmuskelphysiologie und Molekulare Kardiologie, Klinik III für Innere Medizin, Köln, Germany

    Klara Brixius, Konrad F. Frank, Birgit Bölck, Felix Hoyer & Robert H. G. Schwinger

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  1. Klara Brixius
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  2. Konrad F. Frank
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  3. Birgit Bölck
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  4. Felix Hoyer
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  5. Robert H. G. Schwinger
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Correspondence to Robert H. G. Schwinger.

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Brixius, K., Frank, K., Bölck, B. et al. Reverses Remodeling der intrazellulären Ca2+-Homöostase: Neue Konzepte zur Pathophysiologie und Therapie der Herzinsuffizienz. Wien Med Wochenschr 156, 209–215 (2006). https://doi.org/10.1007/s10354-005-0239-4

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  • DOI: https://doi.org/10.1007/s10354-005-0239-4

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