title: Do KV7.1 channels contribute to control of arterial vascular tone?
abstract: KV7.1 voltage-gated potassium channels are expressed in vascular smooth muscle cells (VSMC) of diverse arteries, including mesenteric arteries. Based on pharmacological evidence using R-L3 (KV7.1 channel opener), HMR1556, chromanol 293B (KV7.1 channel blockers), stimulation of these channels has been suggested to evoke profound relaxation in various vascular beds of rats. However, the specificity of these drugs in vivo is uncertain.
  
  
  
  We used Kcnq1-/-mice and pharmacological tools to determine whether KV7.1 channels play a role in the regulation of arterial tone.
  
  
  
  R-L3 produced similar concentration-dependent relaxations (EC50~ 1.4 μM) of arteries from wild-type (Kcnq1+/+) and Kcnq1-/-mice, pre-contracted with either phenylephrine or 60 mM KCl. This relaxation was not affected by 10 μM chromanol 293B, 10 μM HMR1556 or 30 μM XE991 (pan-KV7 channel blocker). The anti-contractile effects of the perivascular adipose tissue (PVAT) were normal in Kcnq1-/-arteries. Chromanol 293B and HMR1556 did not affect the anti-contractile effects of (PVAT). Isolated VSMCs from Kcnq1-/-mice exhibited normal peak KVcurrents. The KV7.2-5 channel opener retigabine caused similar relaxations in Kcnq1-/-and wild-type vessels.
  
  
  
  We conclude that KV7.1 channels were apparently not involved in the control of arterial tone by α1-adrenoceptor agonists and PVAT. In addition, R-L3 is an inappropriate pharmacological tool for studying the function of native vascular KV7.1 channels in mice.
authors.affiliation: Experimental and Clinical Research Center (ECRC), A Joint Cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.|Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics and Interfaculty Center of Pharmacogenomics and Drug Research, University of Tübingen, Tübingen, Germany.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Tsvetkov
authors.affiliation: Experimental and Clinical Research Center (ECRC), A Joint Cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Kaßmann
authors.affiliation: Experimental and Clinical Research Center (ECRC), A Joint Cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Tano
authors.affiliation: Experimental and Clinical Research Center (ECRC), A Joint Cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.|Xiamen Zhongshan Hospital, Xiamen University, Xiamen, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Experimental and Clinical Research Center (ECRC), A Joint Cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Schleifenbaum
authors.affiliation: Department of Cardiology, Vascular Medicine and Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: Voelkl
authors.affiliation: Department of Cardiology, Vascular Medicine and Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.affiliation: School of Biomedical Sciences, 223A, Lo Kwee-Seong Integrated Biomedical Sciences Building, Area 39, Chinese University of Hong Kong, Sha Tin, Hong Kong.
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Experimental and Clinical Research Center (ECRC), A Joint Cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.|Medical Clinic for Nephrology and Internal Intensive Care, Campus Virchow, Charité University Medicine, Berlin, Germany.
authors.forename: Maik
authors.initials: M
authors.lastname: Gollasch
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D051657:KCNQ1 Potassium Channel / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010880:Piperidines / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000494:pharmacology; D014105:Tosyl Compounds / Q000494:pharmacology
chemical_list: C576869:(R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide; D051657:KCNQ1 Potassium Channel; C496910:Kcnq1 protein, mouse; D010880:Piperidines; D013844:Thiazoles; D014105:Tosyl Compounds