![]() The cytoplasmic Ca 2+ concentrations during systole and diastole can differ by a factor of up to 100 (10 μM, 100 nM) and are subject to physiological and pharmacological regulation ( 2– 4, 12, 28). Relaxation follows the reuptake of Ca 2+ ions into the sarcoplasmic reticulum or removal across the plasma membrane via sodium-calcium exchanger. Development of contractile force is driven by an increase in cytoplasmic Ca 2+ concentration from sarcoplasmic Ca 2+ stores ( 9, 17, 35). Finally, this study confirms that fura-2 has Ca 2+ buffering effects and is thereby changing the force response to extracellular Ca 2+.Ĭontractile force is a fundamental physiological parameter of cardiomyocyte function and can be evaluated in heart tissue, isolated papillary muscles, or force-generating engineered heart tissue (EHT). In contrast, no difference in myofilament Ca 2+ sensitivity was detected between skinned rat and human EHTs, suggesting that the difference in sensitivity to external Ca 2+ concentration is due to changes in Ca 2+ handling proteins. Ca 2+ 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 < 0.001) and different sensitivity to external Ca 2+ (EC 50: 0.15, 0.39, and 1.05 mM Ca 2+ in rat, mouse, and human, respectively P < 0.001) in the three groups. Measurements in EHTs under increasing concentrations of extracellular Ca 2+ and responses to isoprenaline and carbachol demonstrate that EHTs recapitulate basic principles of heart tissue functional biology. This article describes an automated technology to perform sequential analysis of contractile force and Ca 2+ 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. The analysis of contractile function and Ca 2+ transients is therefore important to discriminate between myofilament responsiveness and changes in Ca 2+ homeostasis. They reflect the response of the contractile machinery to the systolic increase and diastolic decrease of the cytoplasmic Ca 2+ concentration. Contraction and relaxation are fundamental aspects of cardiomyocyte functional biology.
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