Altered Intracellular Calcium Homeostasis and Arrhythmogenesis in the Aged Heart.
Shanna HamiltonDmitry TerentyevPublished in: International journal of molecular sciences (2019)
Aging of the heart is associated with a blunted response to sympathetic stimulation, reduced contractility, and increased propensity for arrhythmias, with the risk of sudden cardiac death significantly increased in the elderly population. The altered cardiac structural and functional phenotype, as well as age-associated prevalent comorbidities including hypertension and atherosclerosis, predispose the heart to atrial fibrillation, heart failure, and ventricular tachyarrhythmias. At the cellular level, perturbations in mitochondrial function, excitation-contraction coupling, and calcium homeostasis contribute to this electrical and contractile dysfunction. Major determinants of cardiac contractility are the intracellular release of Ca2+ from the sarcoplasmic reticulum by the ryanodine receptors (RyR2), and the following sequestration of Ca2+ by the sarco/endoplasmic Ca2+-ATPase (SERCa2a). Activity of RyR2 and SERCa2a in myocytes is not only dependent on expression levels and interacting accessory proteins, but on fine-tuned regulation via post-translational modifications. In this paper, we review how aberrant changes in intracellular Ca2+ cycling via these proteins contributes to arrhythmogenesis in the aged heart.
Keyphrases
- heart failure
- atrial fibrillation
- left ventricular
- smooth muscle
- protein kinase
- catheter ablation
- blood pressure
- reactive oxygen species
- left atrial
- cardiovascular disease
- oral anticoagulants
- poor prognosis
- acute heart failure
- skeletal muscle
- cardiac resynchronization therapy
- air pollution
- endoplasmic reticulum
- coronary artery disease
- binding protein
- energy transfer
- room temperature