Wide Spectrum of Inhibitory Effects of Sertraline on Cardiac Ion Channels

Abstract

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 µM, respectively. In addition to K+ channels, sertraline also inhibited INa and ICa, and the IC50 values are 6.1 and 2.6 µM, 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.

Use of selective serotonin re‐uptake inhibitors and the heart rate corrected QT interval in a real‐life setting: the population‐based Rotterdam Study

“…For the individual SSRIs, this study is in line with a large cross‐sectional study that used electronic health care records , but is at variance with other, often smaller, studies . Except for fluvoxamine, all other SSRIs have been listed to have QT c ‐prolonging properties , and have been observed to have the potential to block the HERG channel . This discrepancy might be explained by variation in patient populations or by a too low number of users of specific SSRIs in some of these studies, including ours.…”

“…One of the drug classes for which QT c prolonging properties are currently under debate, is selective serotonin re‐uptake inhibitors (SSRIs). In vitro studies reported that a large number of the individual SSRIs have the potential to block the hERG channel , which could consequently increase the QT c . In line with this, many SSRIs are already listed as having QT c prolonging properties , which suggests that SSRIs as a class might increase QT c .…”

Post-SSRI Sexual Dysfunction: A Bioelectric Mechanism?

“…This could be due to effects on the electrogenic serotonin transporter SERT or perhaps upon one or more of several ion channels. [60][61][62][63][64] Because the basic bioelectric circuitry is highly conserved, animal models can serve as an important context within which to understand clinically relevant persistent physiological states induced by transient drug exposure. Thus, we examined the possibility of SSRI-induced long-term changes, which could provide a mechanism for the post-SSRI syndrome in human patients, in a tractable model system: planaria.…”

Taxifolin Glycoside Blocks Humanether-a-go-goRelated Gene K+Channels

“…Loss of function or blockade of the hERG K + channel can induce long QT syndrome (LQTS), which is characterized by a prolonged QT interval on an electrocardiogram and can result in fatal arrhythmias such as torsade de pointes [7,8]. Many drugs have reported side effects, including hERG K + current inhibition, which can lead to acquired LQTS [9-12]. However, little information is available regarding the anti-arrhythmic effect and hERG K + channel blockade that are caused by taxifolin glycoside.…”