Heteromultimeric Kv1 Channels Contribute to Myogenic Control of Arterial Diameter

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 Kvα subunits, Kv1.2, Kv1.4, Kv1.5, and Kv1.6, were identified and confirmed at the protein level with subunit-specific antibodies. Kvβ transcript (β1.1, β1.2, β1.3, and β2.1) expression was also identified. Kv1.5 message was ≈2-fold more abundant than that for Kv1.2 and Kv1.6. Transcripts encoding these three Kv1α subunits were ≈2-fold more abundant in 1st/2nd order conduit compared with 4th order resistance RMAs, and Kvβ1 was 8-fold higher than Kvβ2 message. RMA KDR activated positive to −50 mV, exhibited incomplete inactivation, and were inhibited by 4-AP and correolide. However, neither α-dendrotoxin or κ-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 Kvβ1.2 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.