Negative chronotropic and inotropic effects of lubiprostone on iPS cell-derived cardiomyocytes via activation of CFTR

Figures

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  Fig. 1. Generation of cardiomyocytes from iPS cells. a: Time course for the generation of cardiomyocytes (CMs). b: Undifferentiated mouse iPS cells and iPS-CMs. Left panel: phase contrast Right panel: Nanog-promoter-driven GFP. Bars indicate 100 μm. c: RT-PCR analysis of gene expression in undifferentiated iPS cells, iPS-CMs, and the heart, using specific primers to identify undifferentiated markers, CM markers, chloride channel markers, and a ubiquitous housekeeping gene, β-actin, as indicated in the left column. d: Immunocytochemistry of iPS-CMs, FCMs, and ACMs using cTnI and Cx43 antibodies. Bars indicate 50 μm

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  Fig. 2. Beating response to chemical compounds. a and b: Changes in the beating rate of iPS-CMs treated with 10 μM NDP (a) (n = 5) and 400 nM ISP (b) (n = 7). c and d: Changes in the beating rate of FCMs treated with 10 μM NDP (c) (n = 5) and 400 nM ISP (d) (n = 7). e–g: Changes in the beating rate of iPS-CMs treated with 5 μM LBP, 10 μM CdCl2, or 5 μM GlyH (n = 10). h–j: Changes in the beating rate of FCMs treated with 5 μM LBP, 10 μM CdCl2, or 5 μM GlyH (n = 10). Data are expressed as the mean ± SD. (**P < 0.01 and *P < 0.05 vs. control)

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  Fig. 3. Contraction response to chemical compounds. a and b: Changes in the contraction ratio of iPS-CMs (a) and ACMs (b) treated with ISP at various concentrations. c and d: Changes in the contraction ratio of iPS-CMs (c) and ACMs (d) treated with various concentrations of LBP. e and f: Changes in the contraction ratio of iPS-CMs (e) and ACMs (f) treated with 5 μM LBP, 10 μM CdCl2, or 5 μM GlyH. Data are expressed as the mean ± SD. (n = 10, **P < 0.01 and *P < 0.05 vs. control)

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  Fig. 4. Mechanisms of lubiprostone action on iPS-CMs. Lubiprostone decreased the beating rate and contraction ratio of iPS-CMs due to the activation of CFTR and the increase in CFTR protein at the plasma membrane though prostanoid receptor signaling