{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T02:08:30Z","timestamp":1768874910128,"version":"3.49.0"},"reference-count":37,"publisher":"Rockefeller University Press","issue":"4","license":[{"start":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T00:00:00Z","timestamp":1549497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms"},{"start":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T00:00:00Z","timestamp":1549497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["MDA RG 381149"],"award-info":[{"award-number":["MDA RG 381149"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR-42703"],"award-info":[{"award-number":["AR-42703"]}],"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":["AR-63182"],"award-info":[{"award-number":["AR-63182"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,4,1]]},"abstract":"<jats:p>Periodic paralysis is an ion channelopathy of skeletal muscle in which recurrent episodes of weakness or paralysis are caused by sustained depolarization of the resting potential and thus reduction of fiber excitability. Episodes are often triggered by environmental stresses, such as changes in extracellular K+, cooling, or exercise. Rest after vigorous exercise is the most common trigger for weakness in periodic paralysis, but the mechanism is unknown. Here, we use knock-in mutant mouse models of hypokalemic periodic paralysis (HypoKPP; NaV1.4-R669H or CaV1.1-R528H) and hyperkalemic periodic paralysis (HyperKPP; NaV1.4-M1592V) to investigate whether the coupling between pH and susceptibility to loss of muscle force is a possible contributor to exercise-induced weakness. In both mouse models, acidosis (pH 6.7 in 25% CO2) is mildly protective, but a return to pH 7.4 (5% CO2) unexpectedly elicits a robust loss of force in HypoKPP but not HyperKPP muscle. Prolonged exposure to low pH (tens of minutes) is required to cause susceptibility to post-acidosis loss of force, and the force decrement can be prevented by maneuvers that impede Cl\u2212 entry. Based on these data, we propose a mechanism for post-acidosis loss of force wherein the reduced Cl\u2212 conductance in acidosis leads to a slow accumulation of myoplasmic Cl\u2212. A rapid recovery of both pH and Cl\u2212 conductance, in the context of increased [Cl]in\/[Cl]out, favors the anomalously depolarized state of the bistable resting potential in HypoKPP muscle, which reduces fiber excitability. This mechanism is consistent with the delayed onset of exercise-induced weakness that occurs with rest after vigorous activity.<\/jats:p>","DOI":"10.1085\/jgp.201812231","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T18:56:33Z","timestamp":1569956193000},"page":"555-566","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Recovery from acidosis is a robust trigger for loss of force in murine hypokalemic periodic paralysis"],"prefix":"10.1085","volume":"151","author":[{"given":"Wentao","family":"Mi","sequence":"first","affiliation":[{"name":"Department of Neurology & Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenfen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0684-9705","authenticated-orcid":true,"given":"Marbella","family":"Quinonez","sequence":"additional","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9315-9429","authenticated-orcid":true,"given":"Marino","family":"DiFranco","sequence":"additional","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8428-3690","authenticated-orcid":true,"given":"Stephen C.","family":"Cannon","sequence":"additional","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 2"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2019,2,7]]},"reference":[{"key":"2023072705440108900_bib1","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1113\/jphysiol.1989.sp017582","article-title":"Intracellular chloride and the mechanism for its accumulation in rat lumbrical muscle","volume":"411","author":"Aickin","year":"1989","journal-title":"J. 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