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αB‐Crystallin R120G variant causes cardiac arrhythmias and alterations in the expression of Ca2+ handling proteins and ER stress in mice

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Clinical and Experimental Pharmacology and Physiology

Published online on


Mutations of αB‐crystallin (CryαB), a small heat shock protein abundantly expressed in cardiac and skeletal muscles, are known to cause desmin‐related myopathies. The CryαB R120G allele has been linked to a familial desminopathy, and in the transgenic mice, causes a sudden death at about 28 weeks of age. To investigate the mechanisms of the sudden cardiac arrest of the CryαB R120G transgenic mice, we prepared the protein samples from the left ventricular tissues of the two different age groups (10 verses 28 weeks), and examined Ca2+ handling proteins. We found that the expression levels of SERCA2,phospholamban, ryanodine receptor 2, and calsequestrin 2 were significantly decreased in the 28‐week old CryαB R120G transgenic mice. In addition, low heart rate variability (HRV) such as heart rate, total power and low frequency was observed,and continuous ECG monitoring uncovered cardiac arrhythmias such as ventricular tachycardia, atrioventricular block and atrial flutter in the 28‐week old CryαB R120G transgenic mice. In contrast, we found that the expression levels of endoplasmic reticulum (ER) degradation enhancing, α‐mannosidase‐like protein (EDEM), inositol requirement 1 (IRE1) and x‐box binding protein 1 (XBP1) were significantly increased in the 28‐week old CryαBR120G transgenic mice, suggesting that the CryαBR120G transgenic mice exhibited an increased ER stress. Together, our data suggest that the CryαB R120G dominant variant induces ER stress and impairs Ca2+ regulation leading to an aging related cardiac dysfunction, arrhythmias and decreased autonomous tone with shortened lifespan. This article is protected by copyright. All rights reserved.