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Regulation of cardiovascular calcium channel activity by post-translational modifications or interacting proteins

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Abstract

Voltage-gated calcium channels are the major pathway for Ca2+ influx to initiate the contraction of smooth and cardiac muscles. Alterations of calcium channel function have been implicated in multiple cardiovascular diseases, such as hypertension, atrial fibrillation, and long QT syndrome. Post-translational modifications do expand cardiovascular calcium channel structure and function to affect processes such as channel trafficking or polyubiquitination by two E3 ubiquitin ligases, Ret finger protein 2 (Rfp2) or murine double minute 2 protein (Mdm2). Additionally, biophysical property such as Ca2+-dependent inactivation (CDI) could be altered through binding of calmodulin, or channel activity could be modulated via S-nitrosylation by nitric oxide and phosphorylation by protein kinases or by interacting protein partners, such as galectin-1 and Rem. Understanding how cardiovascular calcium channel function is post-translationally remodeled under distinctive disease conditions will provide better information about calcium channel–related disease mechanisms and improve the development of more selective therapeutic agents for cardiovascular diseases.

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Funding

This work received funding from the Academic Research Fund (AcRF) tier 2 grant from Singapore Ministry of Education (to T.W.S.), Singapore Ministry of Education NUSMed post-doctoral fellowship (to Z.H.), and NGS PhD scholarship from the National University of Singapore (to K.W.Z.L.).

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  1. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117593, Singapore

    Kelvin Wei Zhern Loh, Mui Cheng Liang, Tuck Wah Soong & Zhenyu Hu

  2. NUS Graduate School for Integrative Sciences and Engineering, Singapore, 117456, Singapore

    Kelvin Wei Zhern Loh & Tuck Wah Soong

  3. Neurobiology Programme, Life Sciences Institute, National University of Singapore, Singapore, 117456, Singapore

    Tuck Wah Soong

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Z.H. and K.W.Z.L. wrote the manuscript with input from M.C.L. (figure/table preparation). T.W.S. critically edited the manuscript. All authors approved the final version of the manuscript.

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Loh, K.W.Z., Liang, M.C., Soong, T.W. et al. Regulation of cardiovascular calcium channel activity by post-translational modifications or interacting proteins. Pflugers Arch - Eur J Physiol 472, 653–667 (2020). https://doi.org/10.1007/s00424-020-02398-x

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