Abstract-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 K1 ) 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 IC 50 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 K1 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. (Circ Res. 1998;83:1224-1231.)uinidine is one of the most commonly used drugs for treatment of both atrial and ventricular rhythm disturbances. 1 Quinidine's efficacy as an antiarrhythmic agent is believed to result from its effects on conduction velocity and repolarization of the cardiac action potential. 1,2 Quinidine's ability to prolong the duration of the cardiac action potential has been attributed to its ability to inhibit several different types of potassium ion channels expressed in mammalian cardiac tissue, including the transient outward K current (I to ), the inwardly rectifying K current (I K1 ), the rapidly activating delayed rectifier (I Kr ), and the ultrarapid delayed rectifier (I Kur ). 3 However, the mechanisms by which quinidine exerts its inhibitory effects on these potassium currents are not understood fully.Previous studies in dog, rabbit, and rat cardiac tissue have documented that the ability of quinidine and other antiarrhythmic agents to alter conduction and repolarization change significantly during postnatal development. 4 -8 Quinidine has been shown to prolong both the QT interval 9 and repolarization 4 of the Purkinje fiber action potential to a significantly greater extent in young canines compared with adult animals. Recent evidence suggests that developmental changes in the effects of antiarrhythmic agents on cardiac tissue may be attributed to age-related changes in drug-channel interactions. 6 -8 For example, quinidine block of rabbit ventricular I to and I K1 has been shown to be significantly different in neonatal versus adult myocytes, with cells from neonates being more sensitive to the action of quinidine than adults. 8 It seems likely that age-related differences in quinidine interaction with cardiac ion channels may also exist in man. Recent clinical studies have d...
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