The mechanisms of adrenergic stimulation of cardiac voltage-gated calcium (CaV) channels have remained elusive. Using proximity proteomics and genetically altered mice, we show that phosphorylation of the CaV channel inhibitor Rad is essential for regulation, by the sympathetic nervous system, of calcium influx, and for augmentation of cardiac contractility.
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References
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Katchman, A. et al. Proteolytic cleavage and PKA phosphorylation of α1C subunit are not required for adrenergic regulation of CaV1.2 in the heart. Proc. Natl Acad. Sci. USA 114, 9194–9199 (2017). This paper demonstrates that PKA phosphorylation and proteolytic cleavage of the C terminus of the CaV channel α1C subunit are not required for adrenergic augmentation of calcium currents in the heart.
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This is a summary of: Papa, A. et al. Rad regulation of CaV1.2 channels controls cardiac fight-or-flight response. Nat. Cardiovasc. Res. https://doi.org/10.1038/s44161-022-00157-y (2022).
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Adrenergic augmentation of cardiac contractility requires Rad phosphorylation. Nat Cardiovasc Res 1, 1138–1139 (2022). https://doi.org/10.1038/s44161-022-00168-9
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DOI: https://doi.org/10.1038/s44161-022-00168-9
