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School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK
This study focused on the hypothesis that KCNA genes (which encode KV
1 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 KV1 subunits as well as KVß1, KV2.1, KV
9.3, BKCa1 and BKCaß1. 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 KV2.1 but less or similar amounts encoding KVß1, KV9.3, BKCa1 and BKCaß1. Patch-clamp recordings from freshly isolated smooth muscle cells revealed dominant KV1 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 may be common to all the gene family and play a functional role in the physiological control of blood pressure.
(Received 24 November 2003;
accepted after revision 16 January 2004;
first published online 23 January 2004)
Corresponding author D. Beech: School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK. Email: d.j.beech{at}leeds.ac.uk
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