Heteromultimeric Kv1 channels contribute to myogenic control of arterial diameter.
Inhibition of vascular smooth muscle (VSM) delayed rectifier K+ channels (K(DR)) by 4-aminopyridine (4-AP; 200 micromol/L) or correolide (1 micromol/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 K(DR) of RMA myocytes was characterized using RT-PCR, real-time PCR, and immunocytochemistry. Transcripts encoding the pore-forming Kvalpha subunits, Kv1.2, Kv1.4, Kv1.5, and Kv1.6, were identified and confirmed at the protein level with subunit-specific antibodies. Kvbeta transcript (beta1.1, beta1.2, beta1.3, and beta2.1) expression was also identified. Kv1.5 message was approximately 2-fold more abundant than that for Kv1.2 and Kv1.6. Transcripts encoding these three Kv1alpha subunits were approximately 2-fold more abundant in 1st/2nd order conduit compared with 4th order resistance RMAs, and Kvbeta1 was 8-fold higher than Kvbeta2 message. RMA K(DR) activated positive to -50 mV, exhibited incomplete inactivation, and were inhibited by 4-AP and correolide. However, neither alpha-dendrotoxin or kappa-dendrotoxin affected RMA K(DR), 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 Kvbeta1.2 in human embryonic kidney 293 cells had biophysical and pharmacological properties similar to those of RMA K(DR). It is concluded that K(DR) channels composed of heteromultimers of Kv1 subunits play a critical role in myogenic control of arterial diameter.
Plane
Frances
F
Smooth Muscle Research Group and CIHR Group in Regulation of Vascular Contractility, Faculty of Medicine, University of Calgary, Canada.
Johnson
Rosalyn
R
Kerr
Paul
P
Wiehler
William
W
Thorneloe
Kevin
K
Ishii
Kuniaki
K
Chen
Tim
T
Cole
William
W
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001704:Biopolymers; D002460:Cell Line; D002536:Cerebral Arteries / Q000033:anatomy & histology* / Q000187:drug effects / Q000378:metabolism; D051668:Delayed Rectifier Potassium Channels; D004546:Elapid Venoms / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D007668:Kidney; D051662:Kv1.1 Potassium Channel; D051663:Kv1.2 Potassium Channel; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D051667:Kv1.6 Potassium Channel; D008297:Male; D008638:Mesenteric Arteries / Q000033:anatomy & histology* / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated / Q000096:biosynthesis / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D051669:Shab Potassium Channels; D013045:Species Specificity; D013314:Stress, Mechanical; D014315:Triterpenes / Q000494:pharmacology; D014655:Vascular Resistance; D014666:Vasomotor System / Q000502:physiology*
D001704:Biopolymers; D051668:Delayed Rectifier Potassium Channels; D004546:Elapid Venoms; C496946:KCNA1 protein, human; C496969:KCNA2 protein, human; C496977:KCNA4 protein, human; C496981:KCNA5 protein, human; C496972:Kcna2 protein, rat; C496979:Kcna4 protein, rat; C496983:Kcna5 protein, rat; D051663:Kv1.2 Potassium Channel; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D051667:Kv1.6 Potassium Channel; D010455:Peptides; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D051669:Shab Potassium Channels; D014315:Triterpenes; C118657:correolide; C081506:dendrotoxin K; D051662:Kv1.1 Potassium Channel; C020273:dendrotoxin; D015761:4-Aminopyridine; D011188:Potassium