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Here, using electrophysiology and myography, we discovered that the KCNQ5 voltage\u2010gated potassium channel mediates vascular smooth muscle relaxant effects of barks used in Native American folk medicine. Bark extracts (1%) from Birch, Cramp Bark, Slippery Elm, White Oak, Red Willow, White Willow, and Wild Cherry each strongly activated KCNQ5 expressed in\n                    <jats:italic>Xenopus<\/jats:italic>\n                    oocytes. Testing of a subset including both the most and the least efficacious extracts revealed that Red Willow, White Willow, and White Oak KCNQ\u2010dependently relaxed rat mesenteric arteries; in contrast, Black Haw bark neither activated KCNQ5 nor induced vasorelaxation. Two compounds common to the active barks (gallic acid and tannic acid) had similarly potent and efficacious effects on both KCNQ5 activation and vascular relaxation, and this together with KCNQ5 modulation by other tannins provides a molecular basis for smooth muscle relaxation effects of Native American folk medicine bark extracts.\n                  <\/jats:p>","DOI":"10.1096\/fj.202200724r","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T11:39:19Z","timestamp":1661254759000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["<scp>KCNQ5<\/scp>\n                    activation by tannins mediates vasorelaxant effects of barks used in Native American botanical medicine"],"prefix":"10.1096","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0057-3541","authenticated-orcid":false,"given":"R\u00edan 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