Open channel block of Kv1.5 currents by citalopram

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 techniqu...

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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
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container_title Acta pharmacologica Sinica
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creator Lee, Hyang Mi
Hahn, Sang June
Choi, Bok Hee
description 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.
doi_str_mv 10.1038/aps.2010.14
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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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>20228830</pmid><doi>10.1038/aps.2010.14</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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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
title Open channel block of Kv1.5 currents by citalopram
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