Fetal and Neonatal Development of Ca2+ Transients and Functional Sarcoplasmic Reticulum in Beating Mouse Hearts

Abstract

Background: It is generally accepted that Ca 2+ -induced Ca 2+ 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 2+ transients using whole hearts of mouse embryos and neonates. Methods and Results:Fluo-3 fluorescence signals from stimulated whole hearts were detected using a photomultiplier and stored as Ca 2+ transients. The upstroke and decay of Ca 2+ transients became more rapid from the late embryonic stages to the neonatal stage. After thapsigargin application (an inhibitor of the sarcoplasmic Ca 2+ -ATPase [SERCA]), time to 50% relaxation (T50) of Ca 2+ transients was significantly prolonged. There were no significant changes in T50 after Ru360 application (an inhibitor of mitochondrial Ca 2+ uniporter). The rate of increase in the amplitude of Ca 2+ transients after caffeine application became larger during developmental stages.Conclusions: Ca 2+ homeostasis developmentally changes from a slow rise and decay of Ca 2+ transients to rapid kinetics after the mid-embryonic stage. SERCA began to contribute significantly to Ca 2+ homeostasis at early embryonic stages and sarcoplasmic reticulum Ca 2+ contents increased from embryonic to neonatal stages, whereas mitochondrial Ca 2+ uptake did not contribute to Ca 2+ transients on a beat-to-beat basis. (Circ J 2010; 74: 1442 -1450

Complex restitution behavior and reentry in a cardiac tissue model for neonatal mice

“…; Wang and Sobie ; Korhonen et al ; Kawamura et al. ). Neonatal ventricular myocytes of mice differ from their adult counterparts in a number of properties, including smaller size, greater currents through the Na + /Ca 2+ pump reduced outward K + currents, and reduced role of the SR to calcium release during a systole.…”

“…Species-specific models have been published for a number of species including guinea pig Rudy 1991, 1994), rat (Pandit et al 2001), mouse (Bondarenko et al 2004;Wang and Sobie 2008;Koivum€ aki et al 2009;Li et al 2010), and human (ten Tusscher et al 2004;Bueno-Orovio et al 2008) as it was found to be necessary to account for species-specific differences in current contributions to the AP. More recently, important developmental changes in cardiac electrophysiology of mouse myocytes have been identified (Nuss and Marban 1994;Wang et al 1996;Wetzel and Klitzner 1996;Wang and Duff 1997;Sabir et al 2008;Wang and Sobie 2008;Korhonen et al 2009;Kawamura et al 2010). Neonatal ventricular myocytes of mice differ from their adult counterparts in a number of properties, including smaller size, greater currents through the Na + /Ca 2+ pump reduced outward K + currents, and reduced role of the SR to calcium release during a systole.…”

Phosphorylation of Ser283 enhances the stiffness of the tropomyosin head-to-tail overlap domain

“…references 29, 44]. Phosphorylation-induced enhanced thin filament responsiveness to narrower cellular Ca 2+ concentrations ranges will be advantageous to fetal muscle, where the control of intracellular Ca 2+ -levels may not be fully developed [45–47], and provide compensatory mechanisms in myopathic muscle [48], where Ca 2+ metabolism may be compromised.…”

Contribution of Sarcoplasmic Reticulum Ca2+ Release and Ca2+ Transporters on Sarcolemmal Channels to Ca2+ Transient in Fetal Mouse Heart

“…Fetal mouse whole hearts at ED 10.5, 13.5, and 16.5 were obtained as previously reported (17). Briefly, the hearts were stained by immersion in a 20 M solution of the Ca 2ϩ -sensitive fluorescent indicator Fluo-3 AM (Molecular Probes, Eugene, OR) for 15 min at 37°C.…”

“…Previously, we used fetal mouse whole heart models to examine the effect of a SR Ca 2ϩ ATPase inhibitor on this Ca 2ϩ transient and indicated that Ca 2ϩ reuptake from the SR might be functional even on embryonic day (ED) 12.5 (17). We hypothesized that Ca 2ϩ release from the SR might be responsible for the increase in intracellular Ca 2ϩ concentration even in fetal hearts and that Ca 2ϩ transporters such as TCCs and NCXs might be involved in cardiac contraction in such hearts.…”