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.
Witchel
Harry J
HJ
Cardiovascular Research Laboratories and Department of Physiology, School of Medical Sciences, Bristol, UK. harry.witchel@bris.ac.uk
Pabbathi
Vijay K
VK
Hofmann
Giovanna
G
Paul
Ashok A
AA
Hancox
Jules C
JC
D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D027682:Cation Transport Proteins; D015283:Citalopram / Q000009:adverse effects / Q000494:pharmacology*; D051638:Ether-A-Go-Go Potassium Channels; D005473:Fluoxetine / Q000494:pharmacology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects*; D008133:Long QT Syndrome / Q000139:chemically induced; D008297:Male; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology*
D020746:Calcium Channels, L-Type; D027682:Cation Transport Proteins; D015283:Citalopram; D051638:Ether-A-Go-Go Potassium Channels; D005473:Fluoxetine; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D017367:Selective Serotonin Reuptake Inhibitors; C092509:KCNH6 protein, human