Alterations in the expression of atrial calpains in electrical and structural remodeling during aging and atrial fibrillation

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Abstract

The aim of this study was to investigate the correlation between the change in the expression of atrial calpains and electrical, molecular and structural remodeling during aging and atrial fibrillation (AF). Adult and aged canines in sinus rhythm (SR) and with persistent AF (induced by rapid atrial pacing) were investigated. A whole-cell patch clamp was used to measure the L-type Ca 2+ current (ICa-L) in cells in the left atrium. The mRNA and protein expression of the L-type calcium channel alc subunit (LVDCC a1c) and calpains were measured by quantitative (q)PCR and western blot analysis. Histopathological and ultrastructural changes were analyzed via light and electron microscopy. The quantity of apoptotic myocytes was determined by a terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) assay. In SR groups, atrial cells of the aged canines exhibited a longer action potential (AP) duration to 90% repolarization (APD90), lower AP plateau potential and peak ICa-L current densities (P<0.05). In the adult and aged groups, AF led to a higher maximum diastolic potential, an increase in AP amplitude and decreases in APD90, AP plateau potential and peak ICa-L densities (P<0.05). Compared with the control group, the mRNA and protein expression levels of LVDCCa1c were decreased in the aged groups; however, the mRNA and protein expression of calpain 1 was increased in the adult and the aged groups with AF (P<0.05). Samples of atrial tissue exhibited abnormal histopathological and ultrastructural changes, such as accelerated fibrosis and apoptosis with aging and in AF. Age-related alterations in atrial tissues were attributed to the increased expression of calpain 1. The general pathophysiological alterations in normal aged atria may therefore produce a substrate that is conducive to AF.

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Xu, G. J., Gan, T. Y., Tang, B. P., Chen, Z. H., Mahemuti, A., Jiang, T., … Li, J. X. (2013). Alterations in the expression of atrial calpains in electrical and structural remodeling during aging and atrial fibrillation. Molecular Medicine Reports, 8(5), 1343–1352. https://doi.org/10.3892/mmr.2013.1684

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