Page 8 - Y. Vascular biology

[Y. Vascular biology-5]

Protriptyline, a tricyclic antidepressant, inhibits voltage-

dependent K+ channels in rabbit coronary arterial smooth

muscle cells

Jin Ryeol An¹, Mi Seon Seo¹, Hee Seok Jung¹, Won Sun Park¹

¹Department of Physiology, Kangwon National University School of Medicine, Chuncheon 24341, South Korea

We explore the inhibitory effects of protriptyline, a tricyclic antidepressant drug, on voltage-dependent K+ (Kv)
channels of coronary arterial smooth muscle cells. Protriptyline inhibited the vascular Kv current in a concentration-
dependent manner, with an IC50 value of 5.05 ± 0.97 μM. Protriptyline did not affect the steady-state activation

kinetics. However, the drug shifted the steady-state inactivation curve to the left, suggesting that protriptyline
inhibited the Kv channels by changing their voltage sensitivity. Application of 20 repetitive train pulses (1 or 2 Hz)

progressively increased the protriptyline-induced inhibition of the Kv current, suggesting that protriptyline inhibited
Kv channels in a use (state)-dependent manner. The increase in the inactivation recovery time constant in the

presence of protriptyline also supported use (state)-dependent inhibition of Kv channels by the drug. In the presence
of the Kv1.5 inhibitor, protriptyline did not induce further inhibition of the Kv channels. Thus, we conclude that

protriptyline inhibited the vascular Kv channels in a concentration- and use-dependent manner by changing their
gating properties. Furthermore, protriptyline-induced inhibition of Kv channels mainly involves the Kv1.5.