Objective Many types of vascular smooth muscle cells exhibit prominent delayed rectifier K+ (KDR) currents. These KDR currents may be mediated, at least in part, by KV1.5 channels, which are sensitive to inhibition by diphenyl phosphine oxide-1 (DPO-1). We tested the hypothesis that DPO-1-sensitive KDR channels regulate the tone and reactivity of resistance-sized vessels from rat brain (middle cerebral artery) and skeletal muscle (gracilis artery). Methods Middle cerebral and gracilis arteries were isolated and subjected to three kinds of experimental analysis: a) Western blot/immunocytochemistry; b) patch clamp electrophysiology; and c) pressure myography. Results Western blot and immunocytochemistry experiments demonstrated KV1.5 immunoreactivity in arteries and smooth muscle cells isolated from them. Whole-cell patch clamp experiments revealed smooth muscle cells from resistance-sized arteries to possess a KDR current that was blocked by DPO-1. Resistance arteries constricted in response to increasing concentrations of DPO-1. DPO-1 enhanced constrictions to phenylephrine and serotonin in gracilis and middle cerebral arteries, respectively. When examining the myogenic response, we found that DPO-1 reduced the diameter at any given pressure. Dilations in response to acetylcholine and sodium nitroprusside were reduced by DPO-1. Conclusion We suggest that KV1.5, a DPO-1-sensitive KDR channel, plays a major role in determining microvascular tone and the response to vasoconstrictors and vasodilators.

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