Characteristics of calcium sparks in cardiomyocytes derived from embryonic stem cells

In embryonic stem (ES) cell-derived cardiomyocytes, spontaneous Ca2+ sparks representing Ca2+ release through ryanodine receptor (RyR) channels were characterized and correlated to the expression of RyRs as well as the Ca2+ load of the sarcoplasmic reticulum (SR). In very early developmental stage (VEDS) cardiac precursor cells, global intracellular Ca2+ concentration ([ Ca2+](i)) fluctuations occurred, whereas Ca2+ sparks and contractions were absent. In early developmental stages (EDS), contractions as well as Ca2+ sparks were obvious. During the further differentiation to late developmental stage (LDS) cardiomyocytes, a marked increase in the frequency of global [Ca2+](i) transients, the amplitude and the frequency of Ca2+ sparks, as well as the expression of RyRs and the volume of RyR-positive SR, was observed. Furthermore, the caffeine-releasable SR Ca2+ load was elevated in LDS compared with EDS cardiomyocytes. A high-Ca2+ solution raised spark frequency as well as amplitude in EDS cardiomyocytes to the levels of LDS cardiomyocytes. The characteristics of Ca2+ sparks occurring in cardiomyocytes differentiated from ES cells may be governed by the Ca2+ load of the SR and/or the density of RyRs.