Inhibitory actions of the selective serotonin re‐uptake inhibitor citalopram on HERG and ventricular L‐type calcium currents

FEBS Letters

Witchel, Harry J²  Hancox, Jules C²  Hofmann, Giovanna¹  Pabbathi, Vijay K²  Paul, Ashok A² 

[1] International School for Advanced Studies (SISSA), INFM Unit, Via Beirut 2–4, 34014 Trieste, Italy;Cardiovascular Research Laboratories and Department of Physiology, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK

关键词: Acquired long QT syndrome;    Citalopram;    Early afterdepolarisation;    Fluoxetine;    HERG;    I Ca;    L;    I Kr;    Myocyte;    Rapid delayed rectifier;    Selective serotonin re-uptake inhibitor;    SSRI;    ECG;    electrocardiogram;    EAD;    early afterdepolarisation;    HERG;    human ether-a-go-go related gene;    I Ca;    L;    L-type calcium current;    SSRI;    selective serotonin re-uptake inhibitor;    TCA;    tricyclic antidepressant;   

DOI  :  10.1016/S0014-5793(01)03320-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Using whole-cell patch clamp recording of heterologous HERG-mediated currents in transfected mammalian cells, we observed that the selective serotonin re-uptake inhibitor citalopram blocks HERG with an IC₅₀ of 3.97 μM. This is slightly less potent than fluoxetine in our system (IC₅₀ of 1.50 μM). In isolated guinea pig ventricular cardiomyocytes citalopram inhibited L-type calcium current (I _Ca,L). The voltage dependence of I _Ca,L inactivation in the presence of 100 μM citalopram was shifted significantly leftward. As a result, the I _Ca,L ‘window’ in citalopram was found to be (a) smaller and (b) leftward-shifted compared to control. The effects of citalopram on both calcium current amplitude and the I _Ca,L ‘window’ may help to explain citalopram's good cardiac safety profile, given its propensity to block HERG at excessive dosages.

【 授权许可】

Unknown