Open channel block of Kv1.5 currents by citalopram.
OBJECTIVE
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.


CONCLUSIONS
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.
Department of Pharmacology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-180, Republic of Korea.
Hyang Mi
HM
Lee
Sang June
SJ
Hahn
Bok Hee
BH
Choi
D000818:Animals; D016466:CHO Cells; D015283:Citalopram / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D004594:Electrophysiology; D015870:Gene Expression; D051666:Kv1.5 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D015283:Citalopram; D051666:Kv1.5 Potassium Channel; D017367:Selective Serotonin Reuptake Inhibitors