Characteristics of calcium sparks in cardiomyocytes derived from embryonicstem cells

In embryonic stem (ES) cell-derived cardiomyocytes, spontaneous Ca2+ sparks representing Ca2+ release through ryanodine receptor (RyR) channels were c haracterized and correlated to the expression of RyRs as well as the Ca2+ l oad of the sarcoplasmic reticulum (SR). In very early developmental stage ( VEDS) cardiac precursor cells, global intracellular Ca2+ concentration ([ C a2+](i)) fluctuations occurred, whereas Ca2+ sparks and contractions were a bsent. In early developmental stages (EDS), contractions as well as Ca2+ sp arks 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 wel l 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 com pared with EDS cardiomyocytes. A high-Ca2+ solution raised spark frequency as well as amplitude in EDS cardiomyocytes to the levels of LDS cardiomyocy tes. The characteristics of Ca2+ sparks occurring in cardiomyocytes differe ntiated from ES cells may be governed by the Ca2+ load of the SR and/or the density of RyRs.