Sertraline is a commonly used antidepressant of the selective serotonin reuptake inhibitors (SSRIs) class. In these experiments, we have used the whole cell patch clamp technique to examine the effects of sertraline on the major cardiac ion channels expressed in HEK293 cells and the native voltage-gated Ca2＋ channels in rat ventricular myocytes. According to the results, sertraline is a potent blocker of cardiac K＋ channels, such as hERG, IKs and IK1. The rank order of inhibitory potency was hERG ＞IK1＞IKs with IC50 values of 0.7, 10.5, and 15.2 ՌM, respectively. In addition to K＋ channels, sertraline also inhibited INa and ICa, and the IC50 values are 6.1 and 2.6 ՌM, respectively. Modification of these ion channels by sertraline could induce changes of the cardiac action potential duration and QT interval, and might result in cardiac arrhythmia.