Open channel block of Kv1.5 currents by citalopram

• Published in: Acta pharmacologica Sinica 2010-04, Vol.31 (4), p.429-435
• Main Authors: Lee, Hyang Mi, Hahn, Sang June, Choi, Bok Hee
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; CHO Cells; Citalopram - pharmacology; Cricetinae; Cricetulus; Electrophysiology; Gene Expression; Immunology; Internal Medicine; Kv1.5 Potassium Channel - genetics; Kv1.5 Potassium Channel - metabolism; Medical Microbiology; Original; original-article; Patch-Clamp Techniques; Pharmacology/Toxicology; Rats; Serotonin Uptake Inhibitors - pharmacology; Vaccine; 全细胞膜片钳技术; 时间依赖性; 浓度依赖性; 电压范围; 相互作用; 西酞普兰
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2010.14

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.