Age-associated changes in electrical function of the zebrafish heart

Abstract

Age-associated changes in cardiac structure and function have been observed from the molecular to whole organ level in humans and mammalian models. Understanding the mechanisms involved is important for explaining the development of cardiac disease with age and developing novel strategies for its treatment and prevention. The zebrafish represents a powerful model for cardiovascular research, as various cardiac pathologies have been recapitulated, it is easily genetically modified, and it is a relatively low cost and high-throughput option. In aged zebrafish, myocyte hypertrophy, increased ventricular density and fibrosis, valvular lesions, and reductions in coronary vasculature have been described. The functional consequences of these structural changes however, are relatively unknown. In the current study, we investigated age-related changes in cardiac function in the isolated zebrafish heart. In older animals, heart rate was less stable, sinoatrial node recovery time was increased, and the heart rate response to vagal nerve stimulation was reduced, suggesting an age-dependent change in sinoatrial node function. These changes were accompanied by age-related differences in intracardiac innervation, with the total number and proportion of cholinergic neurons being higher in older animals. In contrast, calcium transient duration was highly variable in young animals, while baseline heart rate and rates of contraction and relaxation were also highly variable, but on average did not change with age. These results suggest that age-associated changes in both myocyte and intracardiac neuronal structure and function exist in the zebrafish heart, offering a new model for studies of cardiac ageing.