Inhibition of Cardiac Ion Channels by Sertraline 331 cells, the malfunction of the INa cause inherited arrhythmo- genic syndromes including long QT syndrome subtype 3 (LQT3), Brugada syndrome, and several cardiac conduction defects (CCD) [30]. Cardiac L-type calcium channel muta- tions can also induce severe arrhythmic disorder [31]. Although SSRIs (e.g. fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, and venlafaxin) are considered to be free from the cardiotoxicity, there are increasing number of case reports on various arrhythmias and syncope asso- ciated with the use of SSRIs including sertraline [32-35]. The study with spontaneously beating isolated guinea-pig atria, the sertraline caused a dose-dependent decrease in the rate contractions and in the contractile force, which de- creased ouabain-induced arrhythmia [36]. According to our present result, this effect probably owes to the inhibition of cardiac Na＋ and Ca2＋ channels. When ECG effects of sertraline were investigated in an adult outpatient population, sertraline had no significant effect on the parameters such as RR, PR, QRS, and QT in- tervals [10]. However, several reports have shown clinically significant QT prolongation during sertraline therapy [37,38]. Recently, the case report for QT interval prolonga- tion after an overdose of sertraline was released [31]. In addition, cardiac arrest [39] and tachycardia [40] during sertaline therapy was also reported on several case. According to this investigation, the QT prolongation and sudden cardiac death can be induced by the effect of sertra- line on several major ion channel of involving cardiac repolarization. Cardiac action potential was made by net of the various ion channels like as K＋ channel terminating action potential duration and Na＋ or Ca2＋ channels pro- longing the action potential duration. Some drugs modified these ion channels could induce change of the cardiac action potential duration and QT interval, resulted in cardiac arrhythmia. However, interactions with multiple cardiac ion channels can either enhance or compromise the pro- longation of action potential duration and QT. Therefore, in general, an integrated assessment of in vitro and in vivo data is required in order to predict the ventricular ar- rhythmogenic risk of a new drug candidate in humans. Taken together with previous in vivo data, the contribu- tion of the inhibitory effects of sertraline on cardiac ion channels to the therapeutic action of sertraline cannot be excluded. Therefore, the patients taking sertraline espe- cially with risks of long QT syndrome should be cautiously monitored for clinical signs of cardiac arrhythmia. ACKNOW LEDGEMENTS This research was supported by the Basic Science Research Program through the National. 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