Published online before print December 23, 2004, doi: 10.1161/01.RES.0000154070.06421.25
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© 2005 American Heart Association, Inc.
Integrative Physiology |
Heteromultimeric Kv1 Channels Contribute to Myogenic Control of Arterial Diameter
From the Smooth Muscle Research Group and CIHR Group in Regulation of Vascular Contractility (F.P., R.J., P.K., W.W., K.T., T.C., W.C.), Faculty of Medicine, University of Calgary, Canada; and Division of Cardiovascular Pharmacology (K.I.), Yamagata University School of Medicine, Japan.
Correspondence to Dr William C. Cole, The Smooth Muscle Research Group, Faculty of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada. E-mail wcole{at}ucalgary.ca
Inhibition of vascular smooth muscle (VSM) delayed rectifier K+ channels (KDR) by 4-aminopyridine (4-AP; 200 µmol/L) or correolide (1 µmol/L), a selective inhibitor of Kv1 channels, enhanced myogenic contraction of rat mesenteric arteries (RMAs) in response to increases in intraluminal pressure. The molecular identity of KDR of RMA myocytes was characterized using RT-PCR, real-time PCR, and immunocytochemistry. Transcripts encoding the pore-forming Kv
subunits, Kv1.2, Kv1.4, Kv1.5, and Kv1.6, were identified and confirmed at the protein level with subunit-specific antibodies. Kvß transcript (ß1.1, ß1.2, ß1.3, and ß2.1) expression was also identified. Kv1.5 message was 
2-fold more abundant than that for Kv1.2 and Kv1.6. Transcripts encoding these three Kv1 subunits were 2-fold more abundant in 1st/2nd order conduit compared with 4th order resistance RMAs, and Kvß1 was 8-fold higher than Kvß2 message. RMA KDR activated positive to –50 mV, exhibited incomplete inactivation, and were inhibited by 4-AP and correolide. However, neither -dendrotoxin or 
-dendrotoxin affected RMA KDR, implicating the presence of Kv1.5 in all channels and the absence of Kv1.1, respectively. Currents mediated by channels because of coexpression of Kv1.2, Kv1.5, Kv1.6, and Kvß1.2 in human embryonic kidney 293 cells had biophysical and pharmacological properties similar to those of RMA KDR. It is concluded that KDR channels composed of heteromultimers of Kv1 subunits play a critical role in myogenic control of arterial diameter.
Key Words: delayed rectifier potassium channel • KCNA • vascular smooth muscle • myogenic contraction • arterial diameter
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