Electrophysiological Characterization of MK886‐Mediated Suppression of Voltage‐Gated K ⁺ Currents in Rabbit Coronary Artery Smooth Muscle Cells

MK886 is a selective inhibitor of 5‐lipoxygenase‐activating protein that suppresses leukotriene synthesis and improves vascular reactivity in rabbit models of endotoxic shock. However, its direct effects on vascular voltage‐gated K + (Kv) channels remain unclear. In this study, we used the whole‐cell patch‐clamp technique to investigate the electrophysiological actions of MK886 on Kv currents in rabbit coronary artery smooth muscle cells. MK886 inhibited Kv currents in a concentration‐dependent manner, with an IC 50 of 0.51 ± 0.23 μM and a Hill coefficient of 0.9 ± 0.14 ( n = 8). While steady‐state activation was not significantly affected, MK886 induced a pronounced leftward shift in the steady‐state inactivation curve, implying preferential binding to the inactivated state of the channel. Consistent with this interpretation, it produced use‐dependent inhibition during repetitive depolarizing pulses at 1 and 2 Hz and significantly slowed recovery from inactivation. Pharmacological dissection using subtype‐selective Kv channel inhibitors revealed that the MK886‐induced inhibition was reduced in the presence of DPO‐1, stromatoxin‐1, and linopirdine compared with MK886 alone. The reduction was more pronounced under DPO‐1 and stromatoxin‐1 conditions, suggesting that Kv1.5‐ and Kv2.1‐related components may contribute to MK886‐induced Kv current inhibition, with possible involvement of Kv7‐related components to a lesser extent. In conclusion, MK886 directly suppresses rabbit coronary artery Kv currents in a concentration‐ and state‐dependent manner by modulating inactivation gating, with substantial involvement of Kv1.5‐ and Kv2.1‐related channel components and possible contribution of Kv7‐related components.