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

• Main Authors: Hongliang Li (Author), Sung Eun Shin (Author), Jin Ryeol An (Author), Mi Seon Seo (Author), Kwon-Soo Ha (Author), Eun-Taek Han (Author), Seok-Ho Hong (Author), Amy L. Firth (Author), Dae-Sung Lee (Author), Mi-Jin Yim (Author), Jeong Min Lee (Author), Grace Choi (Author), Il-Whan Choi (Author), Won Sun Park (Author)
• Format: Book
• Published: Elsevier, 2018-05-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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, Voltage-dependent K+ channel, Coronary artery

Item Description

1347-8613
10.1016/j.jphs.2018.04.005