Fetal and Neonatal Development of Ca^<2+> Transients and Functional Sarcoplasmic Reticulum in Beating Mouse Hearts

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<b><i>Background:</i></b> It is generally accepted that Ca<sup>2+</sup>-induced Ca<sup>2+</sup> release is not the predominant mechanism during embryonic stages. Most studies have been conducted either on primary cultures or acutely isolated cells, in which an apparent reduction of ryanodine receptor density and alterations in the cell shape have been reported. The aim of the present study was to investigate developmental changes in Ca<sup>2+</sup> transients using whole hearts of mouse embryos and neonates. <b><i>Methods and Results:</i></b> Fluo-3 fluorescence signals from stimulated whole hearts were detected using a photomultiplier and stored as Ca<sup>2+</sup> transients. The upstroke and decay of Ca<sup>2+</sup> transients became more rapid from the late embryonic stages to the neonatal stage. After thapsigargin application (an inhibitor of the sarcoplasmic Ca<sup>2+</sup>-ATPase [SERCA]), time to 50% relaxation (T<sub>50</sub>) of Ca<sup>2+</sup> transients was significantly prolonged. There were no significant changes in T<sub>50</sub> after Ru360 application (an inhibitor of mitochondrial Ca<sup>2+</sup> uniporter). The rate of increase in the amplitude of Ca<sup>2+</sup> transients after caffeine application became larger during developmental stages. <b><i>Conclusions:</i></b> Ca<sup>2+</sup> homeostasis developmentally changes from a slow rise and decay of Ca<sup>2+</sup> transients to rapid kinetics after the mid-embryonic stage. SERCA began to contribute significantly to Ca<sup>2+</sup> homeostasis at early embryonic stages and sarcoplasmic reticulum Ca<sup>2+</sup> contents increased from embryonic to neonatal stages, whereas mitochondrial Ca<sup>2+</sup> uptake did not contribute to Ca<sup>2+</sup> transients on a beat-to-beat basis.  (<i>Circ J</i> 2010; <b>74:</b> 1442 - 1450)<br>


  • Circulation Journal

    Circulation Journal 74(7), 1442-1450, 2010-06-25

    The Japanese Circulation Society

References:  40

Cited by:  1


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