{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:21:58Z","timestamp":1787242918175,"version":"build-2736575974"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"13","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR063182"],"award-info":[{"award-number":["AR063182"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR078198"],"award-info":[{"award-number":["AR078198"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["T32AR0659972"],"award-info":[{"award-number":["T32AR0659972"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32GM065823"],"award-info":[{"award-number":["T32GM065823"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR080282"],"award-info":[{"award-number":["AR080282"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:p>\n                    Andersen\u2013Tawil syndrome (ATS) is an ion channelopathy with variable penetrance for the triad of periodic paralysis, arrhythmia, and dysmorphia. Dominant-negative mutations of\n                    <jats:italic>KCNJ2<\/jats:italic>\n                    encoding the Kir2.1 potassium channel subunit are found in 60% of ATS families. As with most channelopathies, episodic attacks in ATS are frequently triggered by environmental stresses: exercise for periodic paralysis or stress with adrenergic stimulation for arrhythmia. Fluctuations in K\n                    <jats:sup>+<\/jats:sup>\n                    , either low or high, are potent triggers for attacks of weakness in other variants of periodic paralysis (hypokalemic periodic paralysis or hyperkalemic periodic paralysis). For ATS, the [K\n                    <jats:sup>+<\/jats:sup>\n                    ] dependence is less clear; with reports describing weakness in high-K\n                    <jats:sup>+<\/jats:sup>\n                    or low-K\n                    <jats:sup>+<\/jats:sup>\n                    . Patient trials with controlled K\n                    <jats:sup>+<\/jats:sup>\n                    challenges are not possible, due to arrhythmias. We have developed two mouse models (genetic and pharmacologic) with reduced Kir currents, to address the question of K\n                    <jats:sup>+<\/jats:sup>\n                    -sensitive loss of force. These animal models and computational simulations both show K\n                    <jats:sup>+<\/jats:sup>\n                    -dependent weakness occurs only when Kir current is &lt;30% of wildtype. As the Kir deficit becomes more severe, the phenotype shifts from high-K\n                    <jats:sup>+<\/jats:sup>\n                    -induced weakness to a combination where either high-K\n                    <jats:sup>+<\/jats:sup>\n                    or low-K\n                    <jats:sup>+<\/jats:sup>\n                    triggers weakness. A K\n                    <jats:sup>+<\/jats:sup>\n                    channel agonist, retigabine, protects muscle from K\n                    <jats:sup>+<\/jats:sup>\n                    -sensitive weakness in our mouse models of the skeletal muscle involvement in ATS.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2418021122","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T13:42:05Z","timestamp":1742996525000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":5,"title":["Potassium-sensitive loss of muscle force in the setting of reduced inward rectifier K\n                    <sup>+<\/sup>\n                    current: Implications for Andersen\u2013Tawil syndrome"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7552-092X","authenticated-orcid":false,"given":"Nathaniel","family":"Elia","sequence":"first","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine at University of California","place":["Los Angeles"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0684-9705","authenticated-orcid":false,"given":"Marbella","family":"Qui\u00f1onez","sequence":"additional","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine at University of California","place":["Los Angeles"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6078-1952","authenticated-orcid":false,"given":"Fenfen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine at University of California","place":["Los Angeles"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2580-3402","authenticated-orcid":false,"given":"Ekaterina","family":"Mokhonova","sequence":"additional","affiliation":[{"name":"Department of 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Physiology, David Geffen School of Medicine at University of California","place":["Los Angeles"]},{"name":"Department of Neurology, David Geffen School of Medicine at University of California","place":["Los Angeles"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1971.tb06990.x"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410420306"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00342-7"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvac118"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI15183"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310278200"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.111.962316"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15369"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab445"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c140062"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/164_2017_52"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410350313"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.2.160"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1514282112"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.283648"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/BFb0116431"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20928"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57398"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66091"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-010-0814-4"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.23293"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.71588"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811277106"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00021.2009"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.3109\/15563650.2014.923903"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1983.sp014552"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.37.1.32"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac441"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(93)81045-2"},{"key":"e_1_3_4_30_2","first-page":"1257","volume-title":"Myology","author":"Lehmann-Horn 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