Nortriptyline, a tricyclic antidepressant, inhibits voltage-dependent K⁺channels in coronary arterial smooth muscle cells

Abstract

We demonstrated the effect of nortriptyline, a tricyclic antidepressant drug and serotonin reuptake inhibitor, on voltage-dependent K+ (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells using a whole-cell patch clamp technique. Nortriptyline inhibited Kv currents in a concentration-dependent manner, with an apparent IC50 value of 2.86±0.52 µM and a Hill coefficient of 0.77±0.1. Although application of nortriptyline did not change the activation curve, nortriptyline shifted the inactivation current toward a more negative potential. Application of train pulses (1 or 2 Hz) did not change the nortriptyline-induced Kv channel inhibition, suggesting that the effects of nortiprtyline were not use-dependent. Preincubation with the Kv1.5 and Kv2.1/2.2 inhibitors, DPO-1 and guangxitoxin did not affect nortriptyline inhibition of Kv channels. From these results, we concluded that nortriptyline inhibited Kv channels in a concentration-dependent and state-independent manner independently of serotonin reuptake.

Inhibition of voltage-dependent K+ current in rabbit coronary arterial smooth muscle cells by the class Ic antiarrhythmic drug propafenone

“…For this reason, the adverse effects of some drugs on vascular Kv channels should be investigated to avoid misinterpretation of clinical/experimental data regarding vascular function. To date, various drugs and chemicals have been reported to inhibit vascular Kv channels independently of their intrinsic functions [ 22 23 ]. Our group recently reported the direct effect of amiodarone, a class III antiarrhythmic drug, on vascular Kv channels using coronary arterial smooth muscle cells [ 24 ].…”

Effect of Nortriptyline on Spreading Depolarization

“…Inhibitory postsynaptic potentials (IPSPs) were applied to the CA1 region of the hippocampus by putting the stimulating electrode on alveus of the hippocampus and activating antidromic post-synaptic activity in this region (20). The concentration of the nortriptyline solution was 100 µM, which is the concentration at which the drug can inhibit the function of many channels (8)(9)(10)(11)(12)(13)(14)(15)(16)21). SD waves were induced by adding one small drop of 3 M KCl (the exact route of induction has been previously discussed (22).…”

“…Finding appropriate ways to control SD, therefore, needs focusing on the behavior of these channels. The classic antidepressant, Nortriptyline, was chosen in this research to study some aspects of the spreading depolarization phenomenon mainly due to its inhibitory effects on voltage-gated (8), Ca 2+ -activated (8) and inwardly rectify-Copyright © 2020, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.…”