Acta Pharmacologica Sinica (2010) 31: 429–435; doi: 10.1038/aps.2010.14; published online 15 Mar 2010

Hyang Mi LEE¹, Sang June HAHN², Bok Hee CHOI^1, *

Aim: To examine whether selective serotonin reuptake inhibitor citalopram interacts with Kv1.5, one of the cardiovascular-specific Kv channel isoforms.

Methods: The interaction between citalopram and Kv1.5 expressed in Chinese hamster ovary cells was studied using the whole-cell patch-clamp technique.   

Results: Citalopram reduced Kv1.5 whole-cell currents in a reversible concentration-dependent manner, with an IC₅₀ value and a Hill coefficient of 2.8±1.1 µmol/L and 0.8±0.3, respectively.  Citalopram-induced inhibition of Kv1.5 is associated with time-dependent development of block without modifying the kinetics of current activation.  The inhibition increased steeply between -30 and 0 mV, which corresponded with the voltage range for channel opening.  In the voltage range positive to 0 mV, inhibition displayed an additional voltage dependence, consistent with an electrical distance δ of 0.19.  Citalopram slowed the deactivation time course, resulting in a tail crossover phenomenon when the tail currents, recorded in the presence and absence of citalopram, were superimposed.  Inhibition of Kv1.5 by citalopram was use-dependent.

Conclusion: The present results suggest that citalopram acts on Kv1.5 currents as an open-channel blocker, and  much caution about arrhythmogenic risk is required when using citalopram in the treatment with depressed patients.

Keywords: citalopram; serotonin reuptake inhibitors; Kv1.5; Shaker-type K⁺ channels; open channel block