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Functional up-regulation of KCNA gene family expression in murine mesenteric resistance artery smooth muscle

  • S. J. Fountain
  • , A. Cheong
  • , R. Flemming
  • , L. Mair
  • , A. Sivaprasadarao
  • , D. J. Beech*
  • *Corresponding author for this work
    • University of Leeds

    Research output: Contribution to journalArticlepeer-review

    Abstract

    This study focused on the hypothesis that KCNA genes (which encode Kvα1 voltage-gated K+ channels) have enhanced functional expression in smooth muscle cells of a primary determinant of peripheral resistance-the small mesenteric artery. Real-time PCR methodology was developed to measure cell type-specific in situ gene expression. Profiles were determined for arterial myocyte expression of RNA species encoding Kvα1 subunits as well as Kvβ1, Kvα2.1, Kvγ9.3, BKCaα1 and BKCaβ1. The seven major KCNA genes were expressed and more readily detected in endothelium-denuded mesenteric resistance artery compared with thoracic aorta; quantification revealed dramatic differential expression of one to two orders of magnitude. There was also four times more RNA encoding Kvα2.1 but less or similar amounts encoding Kvβ1, Kvγ9.3, BKCaα1 and BKCaβ1. Patch-clamp recordings from freshly isolated smooth muscle cells revealed dominant Kvα1 K+ current and current density twice as large in mesenteric cells. Therefore, we suggest the increased RNA production of the resistance artery impacts on physiological function, although there is quantitatively less K+ current than might be expected. The mechanism conferring up-regulated expression of KCNA genes maybe common to all the gene family and play a functional role in the physiological control of blood pressure.

    Original languageEnglish
    Pages (from-to)29-42
    Number of pages14
    JournalJournal of Physiology
    Volume556
    Issue number1
    DOIs
    Publication statusPublished - 30 Mar 2004

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