{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:28:59Z","timestamp":1790605739663,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,2,5]],"date-time":"2017-02-05T00:00:00Z","timestamp":1486252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL67061"],"award-info":[{"award-number":["HL67061"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["094378"],"award-info":[{"award-number":["094378"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL110347"],"award-info":[{"award-number":["HL110347"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Several different voltage\u2010dependent K<jats:sup>+<\/jats:sup> (K<jats:sub>V<\/jats:sub>) channel isoforms are expressed in arterial smooth muscle cells (myocytes).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Vasoconstrictors inhibit K<jats:sub>V<\/jats:sub> currents, but the isoform selectivity and mechanisms involved are unclear.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We show that angiotensin II (Ang II), a vasoconstrictor, stimulates degradation of K<jats:sub>V<\/jats:sub>1.5, but not K<jats:sub>V<\/jats:sub>2.1, channels through a protein kinase C\u2010 and lysosome\u2010dependent mechanism, reducing abundance at the surface of mesenteric artery myocytes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The Ang\u00a0II\u2010induced decrease in cell surface K<jats:sub>V<\/jats:sub>1.5 channels reduces whole\u2010cell K<jats:sub>V<\/jats:sub>1.5 currents and attenuates K<jats:sub>V<\/jats:sub>1.5 function in pressurized arteries.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We describe a mechanism by which Ang\u00a0II stimulates protein kinase C\u2010dependent K<jats:sub>V<\/jats:sub>1.5 channel degradation, reducing the abundance of functional channels at the myocyte surface.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Smooth muscle cells (myocytes) of resistance\u2010size arteries express several different voltage\u2010dependent K<jats:sup>+<\/jats:sup> (K<jats:sub>V<\/jats:sub>) channels, including K<jats:sub>V<\/jats:sub>1.5 and K<jats:sub>V<\/jats:sub>2.1, which regulate contractility. Myocyte K<jats:sub>V<\/jats:sub> currents are inhibited by vasoconstrictors, including angiotensin\u00a0II (Ang\u00a0II), but the mechanisms involved are unclear. Here, we tested the hypothesis that Ang\u00a0II inhibits K<jats:sub>V<\/jats:sub> currents by reducing the plasma membrane abundance of K<jats:sub>V<\/jats:sub> channels in myocytes. Angiotensin\u00a0II (applied for 2\u00a0h) reduced surface and total K<jats:sub>V<\/jats:sub>1.5 protein in rat mesenteric arteries. In contrast, Ang\u00a0II did not alter total or surface K<jats:sub>V<\/jats:sub>2.1, or K<jats:sub>V<\/jats:sub>1.5 or K<jats:sub>V<\/jats:sub>2.1 cellular distribution, measured as the percentage of total protein at the surface. Bisindolylmaleimide (BIM; a protein kinase\u00a0C blocker), a protein kinase\u00a0C inhibitory peptide or bafilomycin\u00a0A (a lysosomal degradation inhibitor) each blocked the Ang\u00a0II\u2010induced decrease in total and surface K<jats:sub>V<\/jats:sub>1.5. Immunofluorescence also suggested that Ang\u00a0II reduced surface K<jats:sub>V<\/jats:sub>1.5 protein in isolated myocytes; an effect inhibited by BIM. Arteries were exposed to Ang\u00a0II or Ang\u00a0II plus BIM (for 2\u00a0h), after which these agents were removed and contractility measurements performed or myocytes isolated for patch\u2010clamp electrophysiology. Angiotensin\u00a0II reduced both whole\u2010cell K<jats:sub>V<\/jats:sub> currents and currents inhibited by Psora\u20104, a K<jats:sub>V<\/jats:sub>1.5 channel blocker. Angiotensin\u00a0II also reduced vasoconstriction stimulated by Psora\u20104 or 4\u2010aminopyridine, another K<jats:sub>V<\/jats:sub> channel inhibitor. These data indicate that Ang\u00a0II activates protein kinase\u00a0C, which stimulates K<jats:sub>V<\/jats:sub>1.5 channel degradation, leading to a decrease in surface K<jats:sub>V<\/jats:sub>1.5, a reduction in whole\u2010cell K<jats:sub>V<\/jats:sub>1.5 currents and a loss of functional K<jats:sub>V<\/jats:sub>1.5 channels in myocytes of pressurized arteries.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp272893","type":"journal-article","created":{"date-parts":[[2016,12,13]],"date-time":"2016-12-13T13:06:59Z","timestamp":1481634419000},"page":"1607-1618","source":"Crossref","is-referenced-by-count":15,"title":["Angiotensin II reduces the surface abundance of K<sub>V<\/sub>1.5 channels in arterial myocytes to stimulate vasoconstriction"],"prefix":"10.1113","volume":"595","author":[{"given":"Michael W.","family":"Kidd","sequence":"first","affiliation":[{"name":"University of Tennessee Health Science Center  Memphis TN 38163 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Bulley","sequence":"additional","affiliation":[{"name":"University of Tennessee Health Science Center  Memphis TN 38163 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1505-3335","authenticated-orcid":false,"given":"Jonathan H.","family":"Jaggar","sequence":"additional","affiliation":[{"name":"University of Tennessee Health Science Center  Memphis TN 38163 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