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

Publication date: May 2018Source: Journal of Pharmacological Sciences, Volume 137, Issue 1Author(s): Hongliang Li, Sung Eun Shin, Jin Ryeol An, Mi Seon Seo, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Amy L. Firth, Dae-Sung Lee, Mi-Jin Yim, Jeong Min Lee, Grace Choi, Il-Whan Choi, Won Sun ParkAbstractWe 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.

Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research