Age-related changes of action potential plateau shape in isolated human atrial fibers

Because the frequency of atrial arrhythmia increases dramatically with age in humans, we investigated age-related changes of cellular electrical activity in human atrial fibers, utilizing standard microelectrode techniques. Twenty-four atrial samples, uniformly exhibiting fast responses, were selected. Patients were in two different age groups: 10.0 +/- 7.0 mo and 54.4 +/- 9.7 yr. Although mean maximum diastolic electrical potential did not significantly differ, the two groups showed marked dissimilarities in action potential (AP) shape. Adult-type APs always exhibited an initial notch followed by a low-level prolonged plateau, whereas APs of the young were more triangular and had a short plateau approaching zero potential. 4-Aminopyridine (0.5 mM) markedly increased the level of the adult AP plateau without suppressing the initial notch, which disappeared after further addition of caffeine (10 mM). The simultaneous action of the two drugs changed an adult-type AP into a young type. The drug effects were much less marked in young atria. Our results suggest that an age-related increase in transient outward currents can account for the differences in plateau shape described. Moreover, age-related differences in plateau configuration in response to a period of rest suggest a faster repriming kinetic of these currents in adults.