Hyang Mi Lee1, Sang June Hahn, Bok Hee Choi. 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.
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 depressedpatients.
Authors: R Swanson; J Marshall; J S Smith; J B Williams; M B Boyle; K Folander; C J Luneau; J Antanavage; C Oliva; S A Buhrow Journal: Neuron Date: 1990-06 Impact factor: 17.173
Authors: Han Sol Kim; Hongliang Li; Hye Won Kim; Sung Eun Shin; Mi Seon Seo; Jin Ryeol An; Kwon-Soo Ha; Eun-Taek Han; Seok-Ho Hong; Il-Whan Choi; Grace Choi; Dae-Sung Lee; Won Sun Park Journal: Korean J Physiol Pharmacol Date: 2017-06-26 Impact factor: 2.016