Korean J Physiol Pharmacol.  2023 Jul;27(4):399-406. 10.4196/kjpp.2023.27.4.399.

Encainide, a class Ic anti-arrhythmic agent, blocks voltage-dependent potassium channels in coronary artery smooth muscle cells

• Li H
• Zhou Y
• Yang Y
• Zha Y
• Ye B
• Mun SY
• Zhuang W
• Liang J
• Park WS

• KMID: 2544141
• DOI: http://doi.org/10.4196/kjpp.2023.27.4.399

Abstract

Voltage-dependent K + (Kv) channels are widely expressed on vascular smooth muscle cells and regulate vascular tone. Here, we explored the inhibitory effect of encainide, a class Ic anti-arrhythmic agent, on Kv channels of vascular smooth muscle from rabbit coronary arteries. Encainide inhibited Kv channels in a concentration-dependent manner with an IC₅₀ value of 8.91 ± 1.75 μM and Hill coefficient of 0.72 ± 0.06. The application of encainide shifted the activation curve toward a more positive potential without modifying the inactivation curve, suggesting that encainide inhibited Kv channels by altering the gating property of channel activation. The inhibition by encainide was not significantly affected by train pulses (1 and 2 Hz), indicating that the inhibition is not use (state)-dependent. The inhibitory effect of encainide was reduced by pretreatment with the Kv1.5 subtype inhibitor. However, pretreatment with the Kv2.1 subtype inhibitor did not alter the inhibitory effects of encainide on Kv currents. Based on these results, encainide inhibits vascular Kv channels in a concentration-dependent and use (state)-independent manner by altering the voltage sensor of the channels. Furthermore, Kv1.5 is the main Kv subtype involved in the effect of encainide.

Keyword

Anti-arrhythmia agents; Coronary vessels; Electrophysiology; Kv1.5 potassium channel; Potassium channels, voltage-gated