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In addition to diabetes, DEND patients present muscle weakness as one of the symptoms, and although the muscle weakness is considered to originate in the brain, the pathological effects of mutated K<jats:sub>ATP<\/jats:sub> channels in skeletal muscle remain elusive. Here, we describe the local effects of the K<jats:sub>ATP<\/jats:sub> channel on muscle by expressing the mutation present in the K<jats:sub>ATP<\/jats:sub> channels of the DEND syndrome in the murine skeletal muscle cell line C2C12 in combination with computer simulation. The present study revealed that the DEND mutation can lead to a hyperpolarized state of the muscle cell membrane, and molecular dynamics simulations based on a recently reported high-resolution structure provide an explanation as to why the mutation reduces ATP sensitivity and reveal the changes in the local interactions between ATP molecules and the channel.<\/jats:p>","DOI":"10.1038\/s41598-021-86121-5","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T11:04:44Z","timestamp":1616497484000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Structure based analysis of KATP channel with a DEND syndrome mutation in murine skeletal muscle"],"prefix":"10.1038","volume":"11","author":[{"given":"Shoichiro","family":"Horita","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyuki","family":"Ono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saul","family":"Gonzalez-Resines","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Ono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megumi","family":"Yamachi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songji","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Domene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Maejima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenju","family":"Shimomura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,23]]},"reference":[{"key":"86121_CR1","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/S1084-2756(03)00064-2","volume":"9","author":"M Polak","year":"2004","unstructured":"Polak, M. & Shield, J. 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