CaMK II in Cardiovascular Diseases, Especially CaMK II-δ: Friends or Enemies

Figures

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  Figure 1. Domain structures of CaMK II. CaMK II, Ca2+/calmodulin-dependent kinase II. The primary structure of CaMK II contains an N-terminal kinase domain, a catalytic domain, a middle regulatory region, and a tail C-terminal association domain.

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  Figure 2. CAMK II-mediated arrhythmias by acting on sodium channel. CaMK II can phosphorylate NaV1.5 channels, increase INa L, cause sodium overload, prolong the APD, and produce EAD. Activation of the NCX causes calcium overload and induces arrhythmias.

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  Figure 3. CAMK II-mediated arrhythmias by acting on calcium channel. CaMK II can activate the expression of the CaV1.2 in the heart. ROS can increase Ca2+ influx, trigger SR Ca2+ release through calcium channels, and increase intracellular Ca2+ and CaMK II activity. It can increase CaMK II activity, thereby inducing EAD and causing arrhythmias.

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  Figure 4. The mechanism of CaMK II in I/R injury. I/R injury, Ca2+ influx, trigger the opening of mPTP, and promote oxidative stress injury. RIPK3 leads to cardiomyocyte necrosis by activating CaMKII. CaMKII-δC aggravates myocardial injury after I/R, whereas CaMK II-δB has a protective effect on the myocardium, and its differential effect can be achieved through its action on NF-κB or TNF-α.

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  Figure 5. The mechanism of CaMK II in cardiac hypertrophy. After Ang II treatment, the Ca2+ concentration is increased, and TRPV3 is activated, which promotes the expression of calcineurin and pCaMK II, enhances the NFAT3, thereby reducing myocardial hypertrophy.