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Human embryonic stem cell–derived cardiomyocytes can mobilize 1,4,5‐inositol trisphosphate–operated [Ca 2+ ] i stores
Author(s) -
Sedan Oshra,
Dolnikov Katya,
ZeeviLevin Naama,
Fleishmann Noa,
Spiegel Idit,
Berdichevski Sasha,
Amit Michal,
ItskovitzEldor Joseph,
Binah Ofer
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.05085.x
Subject(s) - inositol , inositol trisphosphate , microbiology and biotechnology , receptor , intracellular , embryonic stem cell , inositol trisphosphate receptor , calcium signaling , chemistry , endocrinology , medicine , biology , biochemistry , gene
Because previous findings showed that in human embryonic stem cell–derived cardiomyocytes (hESC‐CM) the machinery for Ca 2+ ‐induced release of calcium is immature, we tested the hypothesis that hESC‐CM contain functional 1,4,5‐inositol triphosphate (IP 3 )–operated intracellular Ca 2+ ([Ca 2+ ] i ) stores. We investigated the effects of angiotensin II (AT‐II) and endothelin 1 (ET‐1), which activate the 1,4,5‐IP 3 pathway, on [Ca 2+ ] i transients and contractions in hESC‐CM. Our major findings were that in hESC‐CM, both AT‐II (10 −9 –10 −7 M) and ET‐1 (10 −9 –10 −7 M) exert inotropic and lusitropic effects. The involvement of 1,4,5‐IP 3 ‐dependent intracellular Ca 2+ release in AT‐I–induced effects was supported by these findings: the effects of AT‐II were blocked by 2‐aminoethoxyphenyl borate (2‐APB, a 1,4,5‐IP 3 receptor blocker) and U73122 (a phosopholipase C blocker); and hESC‐CM express AT‐II type 1 and IP 3 type I and II receptors as determined by fluorescence immunostaining. In conclusion, hESC‐CM exhibit functional AT‐II and ET‐1 signaling pathways, as well as 1,4,5‐IP 3 –operated releasable Ca 2+ stores.