Requirement of IP3 receptor 3 (IP3R3) in nitric oxide induced cardiomyocyte differentiation of mouse embryonic stem cells

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

View graph of relations


Related Research Unit(s)


Original languageEnglish
Pages (from-to)9-16
Journal / PublicationExperimental Cell Research
Issue number1
Online published24 Jun 2016
Publication statusPublished - 1 Aug 2016


Nitric oxide (NO) markedly induces cardiomyocyte (CM) differentiation of embryonic stem (ES) cells. Here we examined the role of the Ca2+ signaling in the NO-induced CM differentiation of mouse ES cells. We found that NO induced intracellular Ca2+ increases in ES cells in a dose-dependent manner, and application of IP3 pathway antagonists not only significantly inhibited this induced Ca2+ increase but also abolished NO-induced CM differentiation of ES cells. Subsequently, all 3 types of inositol 1, 4, 5-trisphosphate (IP3) receptors (IP3Rs) in mouse ES cells were individually or triply knocked down. Interestingly, only knockdown of type 3 IP3R (IP3R3) or triple-knockdown of three types of IP3Rs significantly inhibited the NO-induced Ca2+ increases. Consistently, IP3R3 knockdown blocked the NO-induced CM differentiation of ES cells. CMs derived from IP3R3 knockdown ES cells also showed both structural and functional defects. In summary, our results indicate that the IP3R3-Ca2+ pathway is required for NO-induced CM differentiation of ES cells.

Research Area(s)

  • Ca2+, Cardiomyocyte, ES cells, IP3 receptor 3, Nitric oxide