Nortriptyline, a tricyclic antidepressant, inhibits voltage-dependent K+ channels in coronary arterial smooth muscle cells
The Korean Journal of Physiology and Pharmacology
; : 225-232, 2017.
Article
in English
| WPRIM (Western Pacific)
| ID: wpr-728576
Responsible library:
WPRO
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.
Full text:
Available
Database:
WPRIM (Western Pacific)
Main subject:
Serotonin
/
Coronary Vessels
/
Myocytes, Smooth Muscle
/
Muscle, Smooth
/
Nortriptyline
Language:
English
Journal:
The Korean Journal of Physiology and Pharmacology
Year:
2017
Document type:
Article