Quinidine interactions with human atrial potassium channels - Developmental aspects

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 changes 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 quinidine's interaction with major repolarizing currents (I-to, I-Kur, I-ns, and I-Kl) in human atrial myocytes, using the whole-cell configuration of the voltage-clamp technique. Our results indicate that there are age-related changes in both the IC50 for quinidine blockade of I-to, as well as the mechanism of quinidine unblocking. In contrast, quinidine was found to inhibit both adult and pediatric I-Kl and I-Kur in an age-independent manner, whereas the nonselective cation current (I-ns), which contributes to the sustained outward current (I-sus), was insensitive to quinidine. The results from this study help to clarify the electrophysiological mechanism by which quinidine elicits its antiarrhythmic effect in the pediatric and adult human population.