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Received November 24, 2003
Revised December 23, 2003
Accepted after revision January 16, 2004
1 University of Leeds
* To whom correspondence should be addressed. E-mail: d.j.beech{at}leeds.ac.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 KV
1, KV2.1, KV
9.3, BKCa1- and BKCa1. 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
KV1, KV9.3, BKCa1 and BKCa1.
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 potassium-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 critical functional role in
the physiological control of blood pressure.
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