Inhibitory Actions of the Selective Serotonin Re-uptake Inhibitor Citalopram on HERG and Ventricular L-type Calcium Currents

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 IC(50) of 3.97 microM. This is slightly less potent than fluoxetine in our system (IC(50) of 1.50 microM). 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 microM 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.