Hydrogen Peroxide (H2O2) Activates Voltage‐Gated K+ (KV) Channels in Coronary Smooth Muscle Cells

H 2 O 2 has been implicated in flow‐induced dilation, suggested as an endothelium‐derived hyperpolarizing factor, and proposed as a coronary metabolic vasodilator. The mechanisms by which H 2 O 2 elicits vasodilation remain unclear, but effects on smooth muscle membrane potential appear likely. We tested the hypothesis that H 2 O 2 activates K + channels in canine coronary smooth muscle. We determined the effect of H 2 O 2 and specific K + channel blockers on the diameter of cannulated, pressurized arterioles (136 ± 7 μm). H 2 O 2 (10 −8 –10 −3 M) dilated arterioles in a concentration‐dependent manner (96 ± 6%; −logEC 50 = 4.8 ± 0.2). Dilation was reduced to 51 ± 10% and the ‐logEC 50 shifted to 3.1 ± 0.1 with 0.3 mM 4‐aminopyridine (4‐AP), a K V channel blocker. However, dilation was unaffected by 100 nM iberiotoxin (97 ± 3%; −logEC 50 = 4.8 ± 0.1), an inhibitor of Ca 2+ ‐activated K + (BK Ca ) channels. Thus, we determined the effect of H 2 O 2 on K V current using the patch‐clamp technique. H 2 O 2 (1 and 10 mM) significantly increased whole‐cell K + current at 0 mV by 101 ± 25 and 337 ± 36 pA as well as hyperpolarized whole‐cell reversal potential (E rev ) by 7 ± 3 and 17 ± 4 mV, respectively. The effect of H 2 O 2 on whole‐cell K + current and E rev was reversed by 3 mM 4‐AP. These data indicate that H 2 O 2 dilates canine coronary arterioles by activating K V channels and not BK Ca channels, as 4‐AP but not iberiotoxin blocked H 2 O 2 ‐induced vasodilation. Further, H 2 O 2 increased K V current and hyperpolarized E rev , effects that were sensitive to 4‐AP. We suggest that K V channels, or proteins which regulate them, are redox‐sensitive targets in H 2 O 2 ‐induced coronary vasodilation.