title: The ATP-sensitive potassium channel subunit, Kir6.1, in vascular smooth muscle plays a major role in blood pressure control.
abstract: ATP-sensitive potassium channels (KATP) regulate a range of biological activities by coupling membrane excitability to the cellular metabolic state. In particular, it has been proposed that KATP channels and specifically, the channel subunits Kir6.1 and SUR2B, play an important role in the regulation of vascular tone. However, recent experiments have suggested that KATP channels outside the vascular smooth muscle compartment are the key determinant of the observed behavior. Thus, we address the importance of the vascular smooth muscle KATP channel, using a novel murine model in which it is possible to conditionally delete the Kir6.1 subunit. Using a combination of molecular, electrophysiological, in vitro, and in vivo techniques, we confirmed the absence of Kir6.1 and KATP currents and responses specifically in smooth muscle. Mice with conditional deletion of Kir6.1 showed no obvious arrhythmic phenotype even after provocation with ergonovine. However, these mice were hypertensive and vascular smooth muscle cells failed to respond to vasodilators in a normal fashion. Thus, Kir6.1 underlies the vascular smooth muscle KATP channel and has a key role in vascular reactivity and blood pressure control.
authors.affiliation: From The Heart Centre, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom (Q.A., A.M.T., Y.L., K.-E.N., L.G., A.T.); and Department of Medicine, University College London, London, United Kingdom (J.G., R.A., W.R.S., A.T.).
authors.forename: Qadeer
authors.initials: Q
authors.lastname: Aziz
authors.affiliation: From The Heart Centre, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom (Q.A., A.M.T., Y.L., K.-E.N., L.G., A.T.); and Department of Medicine, University College London, London, United Kingdom (J.G., R.A., W.R.S., A.T.).
authors.forename: Alison M
authors.initials: AM
authors.lastname: Thomas
authors.affiliation: From The Heart Centre, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom (Q.A., A.M.T., Y.L., K.-E.N., L.G., A.T.); and Department of Medicine, University College London, London, United Kingdom (J.G., R.A., W.R.S., A.T.).
authors.forename: John
authors.initials: J
authors.lastname: Gomes
authors.affiliation: From The Heart Centre, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom (Q.A., A.M.T., Y.L., K.-E.N., L.G., A.T.); and Department of Medicine, University College London, London, United Kingdom (J.G., R.A., W.R.S., A.T.).
authors.forename: Richard
authors.initials: R
authors.lastname: Ang
authors.affiliation: From The Heart Centre, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom (Q.A., A.M.T., Y.L., K.-E.N., L.G., A.T.); and Department of Medicine, University College London, London, United Kingdom (J.G., R.A., W.R.S., A.T.).
authors.forename: William R
authors.initials: WR
authors.lastname: Sones
authors.affiliation: From The Heart Centre, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom (Q.A., A.M.T., Y.L., K.-E.N., L.G., A.T.); and Department of Medicine, University College London, London, United Kingdom (J.G., R.A., W.R.S., A.T.).
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Li
authors.affiliation: From The Heart Centre, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom (Q.A., A.M.T., Y.L., K.-E.N., L.G., A.T.); and Department of Medicine, University College London, London, United Kingdom (J.G., R.A., W.R.S., A.T.).
authors.forename: Keat-Eng
authors.initials: KE
authors.lastname: Ng
authors.affiliation: From The Heart Centre, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom (Q.A., A.M.T., Y.L., K.-E.N., L.G., A.T.); and Department of Medicine, University College London, London, United Kingdom (J.G., R.A., W.R.S., A.T.).
authors.forename: Lorna
authors.initials: L
authors.lastname: Gee
authors.affiliation: From The Heart Centre, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom (Q.A., A.M.T., Y.L., K.-E.N., L.G., A.T.); and Department of Medicine, University College London, London, United Kingdom (J.G., R.A., W.R.S., A.T.). a.tinker@qmul.ac.uk.
authors.forename: Andrew
authors.initials: A
authors.lastname: Tinker
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004195:Disease Models, Animal; D006973:Hypertension / Q000503:physiopathology; D066298:In Vitro Techniques; D054086:KATP Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D020110:Pinacidil / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D054086:KATP Channels; D014665:Vasodilator Agents; C092520:uK-ATP-1 potassium channel; D020110:Pinacidil; D015740:Calcitonin Gene-Related Peptide
keywords: KATP; blood pressure; muscle, smooth