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

• Published in: The Journal of physiology 2004-04, Vol.556 (1), p.29-42
• Main Authors: Fountain, S. J., Cheong, A., Flemming, R., Mair, L., Sivaprasadarao, A., Beech, D. J.
• Format: Article
• Language: English
• Subjects: Animals; Aorta, Thoracic - metabolism; Electric Conductivity; Gene Expression; Male; Mesenteric Arteries - metabolism; Mesenteric Arteries - physiology; Mice; Mice, Inbred C57BL; Multigene Family; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiology; Myocytes, Smooth Muscle - metabolism; Patch-Clamp Techniques; Potassium Channels - genetics; Potassium Channels - metabolism; Protein Isoforms - genetics; Protein Isoforms - metabolism; Research Papers; RNA - metabolism; Up-Regulation; Vascular Resistance
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2003.058594

This study focused on the hypothesis that KCNA genes (which encode K V α1 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 K V α1 subunits as well as K V β1, K V α2.1, K V γ9.3, BK Ca α1 and BK Ca β1. 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 K V α2.1 but less or similar amounts encoding K V β1, K V γ9.3, BK Ca α1 and BK Caβ 1. Patch-clamp recordings from freshly isolated smooth muscle cells revealed dominant K V α1 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.