L-TYPE CALCIUM CURRENT IN PEDIATRIC AND ADULT HUMAN ATRIAL MYOCYTES -EVIDENCE FOR DEVELOPMENTAL-CHANGES IN CHANNEL INACTIVATION

Animal studies have documented the presence of marked, species-depende nt, developmental changes in the properties of the L-type calcium curr ent in cardiac myocytes. In an effort to understand the postnatal chan ges which occur in the calcium current in human heart, we characterize d the calcium current in atrial myocytes isolated from 17 pediatric an d older children (ages 3 d to 14 y) and 12 adult (ages 43-79 y) human hearts using the whole-cell patch clamp technique. In contrast to anim al models, we found no evidence for age-related changes in calcium cur rent density, steady-state inactivation, or kinetics of recovery from inactivation, suggesting that, in human atrium, calcium channels are i n many aspects functionally mature at the time of birth. However, stat istically significant differences were found in the kinetics of calciu m current inactivation, with calcium current measured in cells isolate d from pediatric human atria inactivating approximately 2-fold faster than cells isolated from adult hearts. These results suggest a possibl e role for age-related changes in calcium current inactivation in the shortened action potential duration observed in pediatric compared wit h adult human atrium.