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

Ibra S. Fancher, Joshua T. Butcher, Steven D. Brooks, Trey S. Rottgen, Paulina R. Skaff, Jefferson C. Frisbee, Gregory M. Dick

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Objective: Many types of vascular smooth muscle cells exhibit prominent KDR currents. These KDR currents may be mediated, at least in part, by KV1.5 channels, which are sensitive to inhibition by DPO-1. We tested the hypothesis that DPO-1-sensitive KDR 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 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 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 KV1.5, a DPO-1-sensitive KDR channel, plays a major role in determining microvascular tone and the response to vasoconstrictors and vasodilators.

Original languageEnglish
Pages (from-to)315-325
Number of pages11
JournalMicrocirculation
Volume22
Issue number4
DOIs
StatePublished - 1 May 2015

Keywords

  • Delayed rectifier potassium current
  • Diphenyl phosphine oxide-1
  • K1.5
  • KCNA5
  • Smooth muscle

Fingerprint Dive into the research topics of 'Diphenyl Phosphine Oxide-1-Sensitive K<sup>+</sup> Channels Contribute to the Vascular Tone and Reactivity of Resistance Arteries From Brain and Skeletal Muscle'. Together they form a unique fingerprint.

  • Cite this