Clinical studies have suggested that quinidine is less effective when used
for the treatment of atrial arrhythmias in pediatric patients compared with
its clinical effectiveness in the adult patient population. Age-related ch
anges in the cardiac actions of quinidine on action potential duration and
interaction with potassium channels in several mammalian species also have
been reported. We investigated the effects of postnatal development on quin
idine's interaction with major repolarizing currents (I-to, I-Kur, I-ns, an
d I-Kl) in human atrial myocytes, using the whole-cell configuration of the
voltage-clamp technique. Our results indicate that there are age-related c
hanges in both the IC50 for quinidine blockade of I-to, as well as the mech
anism of quinidine unblocking. In contrast, quinidine was found to inhibit
both adult and pediatric I-Kl and I-Kur in an age-independent manner, where
as the nonselective cation current (I-ns), which contributes to the sustain
ed outward current (I-sus), was insensitive to quinidine. The results from
this study help to clarify the electrophysiological mechanism by which quin
idine elicits its antiarrhythmic effect in the pediatric and adult human po
pulation.