The Mechanism Underlying Heart Rate and Pacemaking Activity Decline in Developing Sinoatrial Node of the Rabbit Heart

摘要

Diagnosis of heart disease and its treatment are based largely on our understanding of the electrophysiology of adult myocardium. However, the marked difference in the electrical action potential (AP) between neonatal and adult cardiac myocytes suggests a different set of molecular bases in neonatal myocytes, and therefore different treatment for new-borns. In this study we present a new mathematical model of sinoatrial node (SAN) cells of the neonatal rabbit, by modifying densities or kinetics of I_(Na), I_(CaL), I_f, I_(Kr), I_(Ks), and I_(NaCa) in the adult rabbit SAN cell models developed by Zhang et al., based on available experimental data obtained from new-born rabbit SAN cells. The new model reproduced APs similar to experimental recordings from neonatal myocytes, with a faster pacemaking rate. Using the new model, we investigated how age-related changes in ionic currents modulate pacemaking AP morphology, demonstrating the model as a useful tool for testing the effects of drugs on neonatal SAN cells to obtain a better quantitative understanding of differences between neonatal and adult physiology.