Page 6 - Y. Vascular biology

[Y. Vascular biology-4]

The inhibitory effect of anticholinergic drug oxybutynin on

voltage-gated K+ channels in coronary arterial smooth

muscle cells

Jin Ryeol An¹, Won Sun Park¹

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

This study demonstrates the inhibitory effect of anticholinergic drug oxybutynin on voltage-gated K+ (Kv) channels
in rabbit coronary arterial smooth muscle cells. Oxybutynin inhibited vascular Kv channels in a concentration-
dependent manner, with an IC50 value of 11.51 ± 0.38 μM and a Hill coefficient (n) of 2.25 ± 0.12. Application of

oxybutynin shifted the activation curve to the right and the inactivation curve to the left. Pretreatment with the
Kv1.5 subtype inhibitor DPO-1 and the Kv2.1 subtype inhibitor guangxitoxin suppressed the oxybutynin-induced

inhibition of the Kv current. However, application of the Kv7 subtype inhibitor linopirdine did not affect the inhibition
by oxybutynin of the Kv current. The anticholinergic drug atropine did not inhibit the Kv current nor influence

oxybutynin-induced inhibition of the Kv current. From these results, we concluded that oxybutynin suppressed the
vascular Kv current in a concentration-dependent manner by influencing the steady-state activation and inactivation

curves independent of its anticholinergic effect.