A shift of voltage-gated Na+-channel isoforms can contribute to age-dependent remodeling in the mammalian heart

Billur D., Turan B.

Other, pp.75-84, 2022

  • Publication Type: Other Publication / Other
  • Publication Date: 2022
  • Page Numbers: pp.75-84
  • Lokman Hekim University Affiliated: Yes


The prevalence of cardiovascular diseases increases dramatically as the population grow older worldwide. To improve the life of the elderly and prevent age-related cardiac diseases, novel strategies should be undertaken, which include new analysis of processes leading to cardiac aging. The disturbances and abnormalities in cardiac aging can be summarized as functional changes (including remodeling in both the electrical conduction system and vessel system characterized by high blood pressures as well as depressed contraction), structural changes (such as hypertrophy, cardiac lipotoxicity, fibrosis, and abnormal collagen deposition), cellular changes (including loss of several ionic channels, alterations in function of several transporters, exchangers, pumps, increases in the numbers of hypertrophic cardiomyocytes, loss of healthy cardiomyocytes, and senescence cardiomyocytes), molecular changes (including alterations in function of sarcoplasmic reticulum and mitochondria, increase in reactive oxygen species production, and abnormalities in Ca2+-homeostasis). Moreover, since NaV1.5, the major cardiac voltage-gated Na+-channels, plays a central role in the generation of the cardiomyocyte action potential and the propagation of electrical impulses in the heart, here, we document its major role in the aging heart and the contribution of a shift of its isoforms to age-dependent remodeling in the mammalian heart, in addition other ionic currents. From this perspective, the above-mentioned steps are common processes affecting the development of aging cardiac pathophysiology. However, each of these abnormalities alone does not lead to heart dysfunction, hence comorbid chronic conditions are the main factors of an aging heart leading to heart dysfunction. To improve patient care and prevention of age-related cardiac diseases, novel additional insight, including the changes in voltage-gated Na+-channel isoforms, should be gained from the analysis of processes involved and leading to cardiac aging.