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J Pharmacol Sci. 2018 May;137(1):61-66. doi: 10.1016/j.jphs.2018.04.005. Epub 2018 Apr 27.

Blockade of voltage-dependent K+ current in rabbit coronary arterial smooth muscle cells by the tricyclic antidepressant clomipramine.

Author information

1
Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea.
2
Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea.
3
Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea.
4
Institute of Medical Sciences, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea.
5
Department of Pulmonary, Critical Care and Sleep Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA90033, USA.
6
Department of Applied Research, National Marine Biodiversity Institute of Korea, Seocheon, 33662, South Korea.
7
Department of Microbiology, College of Medicine, Inje University, Busan, 48516, South Korea.
8
Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea. Electronic address: parkws@kangwon.ac.kr.

Abstract

We investigated the effect of the tricyclic antidepressant clomipramine on voltage-dependent K+ (Kv) channels in native rabbit coronary arterial smooth muscle cells. Our results showed that clomipramine inhibited vascular Kv channels in a concentration-dependent manner, with an IC50 value of 8.61 ± 4.86 μM and a Hill coefficient (n) of 0.58 ± 0.07. The application of 10 μM clomipramine did not affect the activation curves of the Kv channels; however, the inactivation curves of the Kv channels were shifted toward a more negative potential. The clomipramine-induced inhibition of Kv currents was not changed by the application of train pulses (1 or 2 Hz), which demonstrated that clomipramine inhibited Kv current in a state (use)-independent manner. Pretreatment with the Kv1.5 and Kv2.1 inhibitors, DPO-1 and guangxitoxin, respectively, partially reduced the clomipramine-induced inhibition of Kv currents. Therefore, we concluded that clomipramine inhibited vascular Kv channels in a concentration-dependent, but state (use)-independent manner, regardless of its own function.

KEYWORDS:

Clomipramine; Coronary artery; Voltage-dependent K(+) channel

PMID:
29752209
DOI:
10.1016/j.jphs.2018.04.005
[Indexed for MEDLINE]
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