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. 2021 Aug 27;22(17):9293. doi: 10.3390/ijms22179293

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Ca²⁺ induced Ca²⁺ release mechanism: The cardiac action potential leads to membrane depolarization, thereby opening L-type Ca²⁺ channels (Ca_V1.2). Ca²⁺ in the cytosol then binds to the ryanodine receptor 2 (RyR2) leading to CICR from the sarcoplasmic reticulum (SR) lumen into the cytosol. During systole, the cytosolic Ca²⁺ then binds to troponin C which leads to myocardial contraction. Ca²⁺ in the cytoplasm is returned to the SR via the sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA2a) and its regulatory protein phospholamban (PLB). CM = cardiomyocyte; ECM = extracellular matrix. Image adapted from Priori, S. G., and Chen, S. W. (2011), Circulation Research, 108(7), 871–883 [49].