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Stoehr, Andrea; Neuber, Christiane; Baldauf, Christina; Vollert, Ingra; Friedrich, Felix W.; Flenner, Frederik; Carrier, Lucie; Eder, Alexandra; Schaaf, Sebastian; Hirt, Marc N.; Aksehirlioglu, Bülent; Tong, Carl W.; Moretti, Alessandra; Eschenhagen, Thomas; Hansen, Arne

Automated analysis of contractile force and Ca2+transients in engineered heart tissue

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  • Medientyp: E-Artikel
  • Titel: Automated analysis of contractile force and Ca2+transients in engineered heart tissue
  • Beteiligte: Stoehr, Andrea; Neuber, Christiane; Baldauf, Christina; Vollert, Ingra; Friedrich, Felix W.; Flenner, Frederik; Carrier, Lucie; Eder, Alexandra; Schaaf, Sebastian; Hirt, Marc N.; Aksehirlioglu, Bülent; Tong, Carl W.; Moretti, Alessandra; Eschenhagen, Thomas; Hansen, Arne
  • Erschienen: American Physiological Society, 2014
  • Erschienen in: American Journal of Physiology-Heart and Circulatory Physiology
  • Sprache: Englisch
  • DOI: 10.1152/ajpheart.00705.2013
  • ISSN: 0363-6135; 1522-1539
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p>Contraction and relaxation are fundamental aspects of cardiomyocyte functional biology. They reflect the response of the contractile machinery to the systolic increase and diastolic decrease of the cytoplasmic Ca<jats:sup>2+</jats:sup>concentration. The analysis of contractile function and Ca<jats:sup>2+</jats:sup>transients is therefore important to discriminate between myofilament responsiveness and changes in Ca<jats:sup>2+</jats:sup>homeostasis. This article describes an automated technology to perform sequential analysis of contractile force and Ca<jats:sup>2+</jats:sup>transients in up to 11 strip-format, fibrin-based rat, mouse, and human fura-2-loaded engineered heart tissues (EHTs) under perfusion and electrical stimulation. Measurements in EHTs under increasing concentrations of extracellular Ca<jats:sup>2+</jats:sup>and responses to isoprenaline and carbachol demonstrate that EHTs recapitulate basic principles of heart tissue functional biology. Ca<jats:sup>2+</jats:sup>concentration-response curves in rat, mouse, and human EHTs indicated different maximal twitch forces (0.22, 0.05, and 0.08 mN in rat, mouse, and human, respectively; P &lt; 0.001) and different sensitivity to external Ca<jats:sup>2+</jats:sup>(EC<jats:sub>50</jats:sub>: 0.15, 0.39, and 1.05 mM Ca<jats:sup>2+</jats:sup>in rat, mouse, and human, respectively; P &lt; 0.001) in the three groups. In contrast, no difference in myofilament Ca<jats:sup>2+</jats:sup>sensitivity was detected between skinned rat and human EHTs, suggesting that the difference in sensitivity to external Ca<jats:sup>2+</jats:sup>concentration is due to changes in Ca<jats:sup>2+</jats:sup>handling proteins. Finally, this study confirms that fura-2 has Ca<jats:sup>2+</jats:sup>buffering effects and is thereby changing the force response to extracellular Ca<jats:sup>2+</jats:sup>.</jats:p>
  • Zugangsstatus: Freier Zugang