Calcium spark characteristics in ES cell-derived cardiomyocytes mature during differentiation, driven by increases in SR calcium load and ryanodine receptor density.
Maturation of Ca²⁺ handling in ES cell-derived cardiomyocytes is differentiation-dependent; leaves open translation to human iPSC-CM disease modeling or therapy.
In embryonic stem (ES) cell-derived cardiomyocytes, spontaneous Ca(2+) sparks representing Ca(2+) release through ryanodine receptor (RyR) channels were characterized and correlated to the expression of RyRs as well as the Ca(2+) load of the sarcoplasmic reticulum (SR). In very early developmental stage (VEDS) cardiac precursor cells, global intracellular Ca(2+) concentration ([Ca(2+)](i)) fluctuations occurred, whereas Ca(2+) sparks and contractions were absent. In early developmental stages (EDS), contractions as well as Ca(2+) sparks were obvious. During the further differentiation to late developmental stage (LDS) cardiomyocytes, a marked increase in the frequency of global [Ca(2+)](i) transients, the amplitude and the frequency of Ca(2+) sparks, as well as the expression of RyRs and the volume of RyR-positive SR, was observed. Furthermore, the caffeine-releasable SR Ca(2+) load was elevated in LDS compared with EDS cardiomyocytes. A high-Ca(2+) solution raised spark frequency as well as amplitude in EDS cardiomyocytes to the levels of LDS cardiomyocytes. The characteristics of Ca(2+) sparks occurring in cardiomyocytes differentiated from ES cells may be governed by the Ca(2+) load of the SR and/or the density of RyRs.
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Sauer et al. (2001) studied this question.
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