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The regulation of the small-conductance calcium-activated potassium current and the mechanisms of sex dimorphism in J wave syndrome

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Abstract

Apamin-sensitive small-conductance calcium-activated potassium (SK) current (IKAS) plays an important role in cardiac repolarization under a variety of physiological and pathological conditions. The regulation of cardiac IKAS relies on SK channel expression, intracellular Ca2+, and interaction between SK channel and intracellular Ca2+. IKAS activation participates in multiple types of arrhythmias, including atrial fibrillation, ventricular tachyarrhythmias, and automaticity and conduction abnormality. Recently, sex dimorphisms in autonomic control have been noticed in IKAS activation, resulting in sex-differentiated action potential morphology and arrhythmogenesis. This review provides an update on the Ca2+-dependent regulation of cardiac IKAS and the role of IKAS on arrhythmias, with a special focus on sex differences in IKAS activation. We propose that sex dimorphism in autonomic control of IKAS may play a role in J wave syndrome.

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Funding

This work was supported by the National Natural Science Foundation of China (grant number 81900288), Shanghai Sailing Program, Shanghai, China (grant number 19YF1431900), the National Institutes of Health USA grants R01HL139829 and OT2OD028190, and the Burns and Allen Chair in Cardiology Research of the Cedars-Sinai Medical Center, Los Angeles, CA, USA.

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  1. Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Mu Chen, Yudong Fei, Tai-Zhong Chen & Yi-Gang Li

  2. Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly BLVD, Los Angeles, CA, USA

    Peng-Sheng Chen

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This article is part of the special issue on Calcium Signal Dynamics in Cardiac Myocytes and Fibroblasts: Mechanisms in Pflügers Archiv—European Journal of Physiology

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Chen, M., Fei, Y., Chen, TZ. et al. The regulation of the small-conductance calcium-activated potassium current and the mechanisms of sex dimorphism in J wave syndrome. Pflugers Arch - Eur J Physiol 473, 491–506 (2021). https://doi.org/10.1007/s00424-020-02500-3

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