Diphenyl Phosphine Oxide-1-Sensitive K⁺ Channels Contribute to the Vascular Tone and Reactivity of Resistance Arteries From Brain and Skeletal Muscle

Objective: Many types of vascular smooth muscle cells exhibit prominent K_DR currents. These K_DR currents may be mediated, at least in part, by K_V1.5 channels, which are sensitive to inhibition by DPO-1. We tested the hypothesis that DPO-1-sensitive K_DR channels regulate the tone and reactivity of resistance-sized vessels from rat brain (MCA) and skeletal muscle (GA). Methods: Middle cerebral and gracilis arteries were isolated and subjected to three kinds of experimental analysis: (i) western blot/immunocytochemistry; (ii) patch clamp electrophysiology; and (iii) pressure myography. Results: Western blot and immunocytochemistry experiments demonstrated K_V1.5 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 K_DR current that was blocked by DPO-1. Resistance arteries constricted in response to increasing concentrations of DPO-1. DPO-1 enhanced constrictions to PE 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 ACh and SNP were reduced by DPO-1. Conclusion: We suggest that K_V1.5, a DPO-1-sensitive K_DR channel, plays a major role in determining microvascular tone and the response to vasoconstrictors and vasodilators.