{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:54:10Z","timestamp":1790416450283,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2013,8,22]]},"abstract":"\n Background<\/jats:title>\n \n \n K\n ATP<\/jats:sub>\n <\/jats:styled-content>\n channels, assembled from pore\u2010forming (Kir6.1 or Kir6.2) and regulatory (\n SUR<\/jats:styled-content>\n 1 or\n SUR<\/jats:styled-content>\n 2) subunits, link metabolism to excitability. Loss of Kir6.2 results in hypoglycemia and hyperinsulinemia, whereas loss of Kir6.1 causes Prinzmetal angina\u2013like symptoms in mice. Conversely, overactivity of Kir6.2 induces neonatal diabetes in mice and humans, but consequences of Kir6.1 overactivity are unknown.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We generated transgenic mice expressing wild\u2010type (\n WT<\/jats:styled-content>\n ),\n ATP<\/jats:styled-content>\n \u2010insensitive Kir6.1 [Gly343Asp] (\n GD<\/jats:styled-content>\n ), and\n ATP<\/jats:styled-content>\n \u2010insensitive Kir6.1 [Gly343Asp,Gln53Arg] (\n GD<\/jats:styled-content>\n \u2010\n QR<\/jats:styled-content>\n ) subunits, under Cre\u2010recombinase control. Expression was induced in smooth muscle cells by crossing with\n smooth muscle myosin heavy chain promoter\u2013driven tamoxifen\u2010inducible Cre\u2010recombinase (SMMHC<\/jats:styled-content>\n \u2010Cre\u2010\n ER<\/jats:styled-content>\n ) mice. Three weeks after tamoxifen induction, we assessed blood pressure in anesthetized and conscious animals, as well as contractility of mesenteric artery smooth muscle and\n \n K\n ATP<\/jats:sub>\n <\/jats:styled-content>\n currents in isolated mesenteric artery myocytes. Both systolic and diastolic blood pressures were significantly reduced in\n GD<\/jats:styled-content>\n and\n GD<\/jats:styled-content>\n \u2010\n QR<\/jats:styled-content>\n mice but normal in mice expressing the\n WT<\/jats:styled-content>\n transgene and elevated in Kir6.1 knockout mice as well as in mice expressing dominant\u2010negative Kir6.1 [\n AAA<\/jats:styled-content>\n ] in smooth muscle. Contractile response of isolated\n GD<\/jats:styled-content>\n \u2010QR mesenteric arteries was blunted relative to\n WT<\/jats:styled-content>\n controls, but nitroprusside relaxation was unaffected. Basal\n \n K\n ATP<\/jats:sub>\n <\/jats:styled-content>\n conductance and pinacidil\u2010activated conductance were elevated in\n GD<\/jats:styled-content>\n but not in\n WT<\/jats:styled-content>\n myocytes.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n \n K\n ATP<\/jats:sub>\n <\/jats:styled-content>\n overactivity in vascular muscle can lead directly to reduced vascular contractility and lower blood pressure. We predict that gain of vascular\n \n K\n ATP<\/jats:sub>\n <\/jats:styled-content>\n function in humans would lead to a chronic vasodilatory phenotype, as indeed has recently been demonstrated in Cantu syndrome.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.113.000365","type":"journal-article","created":{"date-parts":[[2013,8,24]],"date-time":"2013-08-24T04:59:22Z","timestamp":1377320362000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":64,"title":["Hypotension Due to Kir6.1 Gain\u2010of\u2010Function in Vascular Smooth Muscle"],"prefix":"10.1161","volume":"2","author":[{"given":"Anlong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO"},{"name":"Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell H.","family":"Knutsen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO"},{"name":"Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Osei\u2010Owusu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Moreno\u2010Dominguez","sequence":"additional","affiliation":[{"name":"Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa M.","family":"Harter","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO"},{"name":"Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Uchida","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, 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