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Imaging cAMP nanodomains in human iPSC-derived cardiomyocytes

Nature Reviews Cardiology (2024)Cite this article

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Cardiac activity is regulated by the β-adrenergic pathway. The activation of this pathway triggers a cellular signalling cascade that increases the production of cAMP, a cyclic nucleotide that activates the enzyme protein kinase A (PKA). PKA phosphorylates key proteins involved in cellular contraction, but can also phosphorylate a multitude of other proteins with different functions. To achieve specific effects, cAMP is confined in nanoscale subcellular domains (nanodomains) close to PKA and its targets. The maintenance and regulation of these nanodomains are central to functional signal transduction, and their dysregulation can result in diseases such as heart failure.

I use this technique in human induced pluripotent stem cell (iPSC)-derived cardiomyocytes to study how the maturation of these cells is affected by a newly identified cAMP nanodomain found at gap junctions, which regulate the communication between adjacent cardiomyocytes. To understand the role of the gap junction-associated cAMP nanodomain in human iPSC-derived cardiomyocytes, endogenous levels of protein expression must be maintained to avoid interference with their maturation process. This technique can more broadly be used to study cAMP nanodomains in which overexpression of the target protein might impair cell physiology. This tool will provide unique insights into the processes involved in human iPSC-derived cardiomyocyte maturation and can also be used to identify new targets in the β-adrenergic pathway that might be relevant for the treatment of diseases, such as heart failure.

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Acknowledgements

The author thanks the J. Zhang laboratory (University of California, San Diego) for providing the FluoStep sensors. She also thanks the British Heart Foundation, cohort Wilson-Olegario, for funding this work.

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  1. University of Oxford, Oxford, UK

    Camille Charrière

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  1. Camille Charrière
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Correspondence to Camille Charrière.

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The author declares no competing interests.

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Charrière, C. Imaging cAMP nanodomains in human iPSC-derived cardiomyocytes. Nat Rev Cardiol (2024). https://doi.org/10.1038/s41569-024-01013-1

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  • DOI: https://doi.org/10.1038/s41569-024-01013-1

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