{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T23:15:56Z","timestamp":1773098156264,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR074985"],"award-info":[{"award-number":["AR074985"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction\/Aims<\/jats:title>\n                    <jats:p>\n                      Hypokalemic periodic paralysis (HypoKPP) is an ion channelopathy causing episodic skeletal muscle weakness triggered by hypokalemia. Reduced inward rectifier K\n                      <jats:sup>+<\/jats:sup>\n                      (Kir) channel activity contributes to membrane depolarization and paralysis, suggesting that pharmacologic activation of muscle K\n                      <jats:sup>+<\/jats:sup>\n                      channels may restore excitability. The Kv7 channel agonist retigabine previously mitigated low\u2010K\n                      <jats:sup>+<\/jats:sup>\n                      weakness in HypoKPP models. Here, we tested whether this effect persists under conditions producing sustained, severe weakness.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Extensor digitorum longus (EDL) muscles from mice homozygous for the\n                      <jats:italic>SCN4A<\/jats:italic>\n                      R669H mutation were studied by isometric twitch force recording at 34\u00b0C, with or without 20\u2009U\/L insulin. Weakness was induced by reducing extracellular K\n                      <jats:sup>+<\/jats:sup>\n                      to 1.0\u2009mM. Retigabine (10\u2009\u03bcM) was applied to the bath, and twitch force was analyzed by paired or unpaired\n                      <jats:italic>t<\/jats:italic>\n                      tests (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094\u20137 per group).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Baseline twitch force in 4.75\u2009mM\u2009K\n                      <jats:sup>+<\/jats:sup>\n                      was ~50% lower in HypoKPP than wild\u2010type muscle (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01). Force declined further after 1\u2009h in 4.75\u2009mM\u2009K\n                      <jats:sup>+<\/jats:sup>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.016) and was completely lost at 1.0\u2009mM\u2009K\n                      <jats:sup>+<\/jats:sup>\n                      with insulin. Retigabine significantly reduced loss of force at both 4.75 and 1.0\u2009mM K\n                      <jats:sup>+<\/jats:sup>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.047 and\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007, respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Kv7 channel activation by retigabine preserved contractile force even during sustained depolarization from severe hypokalemia. These findings extend prior work and support development of K\n                      <jats:sup>+<\/jats:sup>\n                      channel agonists as a therapeutic approach for HypoKPP.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mus.70158","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T10:55:52Z","timestamp":1768820152000},"page":"663-667","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of Retigabine in Treating Weakness in a Mouse Model of Hypokalemic Periodic Paralysis"],"prefix":"10.1002","volume":"73","author":[{"given":"Kirsten","family":"Denman","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Cell Biology and Physiology Wright State University  Dayton Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6956-5531","authenticated-orcid":false,"given":"Mark M.","family":"Rich","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Cell Biology and Physiology Wright State University  Dayton Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2015.tb00630.x"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26009"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10061521"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05598"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.202112946"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20928"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2013.04.004"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-014-2764-0"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.202413610"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199039060-00008"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880130513"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0960-8966(94)00036-9"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac441"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.106580"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/803082"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2019.02.002"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57398"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182886a0e"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201812231"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01267.2006"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66091"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.53.7.1556"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(57)90316-9"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.162800"}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.70158","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mus.70158","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.70158","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T12:47:08Z","timestamp":1773060428000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.70158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,19]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/mus.70158"],"URL":"https:\/\/doi.org\/10.1002\/mus.70158","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,19]]},"assertion":[{"value":"2025-06-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}