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Acta Pharmacol Sin. 2010 Apr;31(4):429-35. doi: 10.1038/aps.2010.14. Epub 2010 Mar 15.

Open channel block of Kv1.5 currents by citalopram.

Author information

1
Department of Pharmacology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-180, Republic of Korea.

Abstract

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 IC(50) value and a Hill coefficient of 2.8+/-1.1 micromol/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 delta 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.

PMID:
20228830
PMCID:
PMC4007671
DOI:
10.1038/aps.2010.14
[Indexed for MEDLINE]
Free PMC Article

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