{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:15:44Z","timestamp":1787008544269,"version":"build-2736575974"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T00:00:00Z","timestamp":1675036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Institutes of Arthritis, Musculoskeletal, and Skin diseases","award":["R01AR063182"],"award-info":[{"award-number":["R01AR063182"]}]},{"name":"National Institutes of Arthritis, Musculoskeletal, and Skin diseases","award":["R01AR078198"],"award-info":[{"award-number":["R01AR078198"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recurrent episodes of weakness in periodic paralysis are caused by intermittent loss of muscle fibre excitability, as a consequence of sustained depolarization of the resting potential. Repolarization is favoured by increasing the fibre permeability to potassium. Based on this principle, we tested the efficacy of retigabine, a potassium channel opener, to suppress the loss of force induced by a low-K+ challenge in hypokalaemic periodic paralysis (HypoPP). Retigabine can prevent the episodic loss of force in HypoPP. Knock-in mutant mouse models of HypoPP (Cacna1s p.R528H and Scn4a p.R669H) were used to determine whether pre-treatment with retigabine prevented the loss of force, or post-treatment hastened recovery of force for a low-K+ challenge in an ex vivo contraction assay. Retigabine completely prevents the loss of force induced by a 2 mM K+ challenge (protection) in our mouse models of HypoPP, with 50% inhibitory concentrations of 0.8 \u00b1 0.13 \u03bcM and 2.2 \u00b1 0.42 \u03bcM for NaV1.4-R669H and CaV1.1-R528H, respectively. In comparison, the effective concentration for the KATP channel opener pinacidil was 10-fold higher. Application of retigabine also reversed the loss of force (rescue) for HypoPP muscle maintained in 2 mM K+. Our findings show that retigabine, a selective agonist of the KV7 family of potassium channels, is effective for the prevention of low-K+ induced attacks of weakness and to enhance recovery from an ongoing loss of force in mouse models of type 1 (Cacna1s) and type 2 (Scn4a) HypoPP. Substantial protection from the loss of force occurred in the low micromolar range, well within the therapeutic window for retigabine.<\/jats:p>","DOI":"10.1093\/brain\/awac441","type":"journal-article","created":{"date-parts":[[2022,11,26]],"date-time":"2022-11-26T17:54:47Z","timestamp":1669485287000},"page":"1554-1560","source":"Crossref","is-referenced-by-count":10,"title":["Retigabine suppresses loss of force in mouse models of hypokalaemic periodic paralysis"],"prefix":"10.1093","volume":"146","author":[{"given":"Marbella","family":"Qui\u00f1onez","sequence":"first","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine at UCLA , Los Angeles, CA 90095 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marino","family":"DiFranco","sequence":"additional","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine at UCLA , Los Angeles, CA 90095 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenfen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine at UCLA , Los Angeles, CA 90095 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8428-3690","authenticated-orcid":false,"given":"Stephen C","family":"Cannon","sequence":"additional","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine at UCLA , Los Angeles, CA 90095 , USA"},{"name":"Department of Neurology, David Geffen School of Medicine at UCLA , Los Angeles, CA 90095 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,1,30]]},"reference":[{"key":"2023041916415153800_awac441-B1","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1002\/cphy.c140062","article-title":"Channelopathies of skeletal muscle excitability","volume":"5","author":"Cannon","year":"2015","journal-title":"Compr Physiol."},{"key":"2023041916415153800_awac441-B2","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1002\/mus.26009","article-title":"Review of the diagnosis and treatment of periodic paralysis","volume":"57","author":"Statland","year":"2018","journal-title":"Muscle Nerve"},{"key":"2023041916415153800_awac441-B3","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s11940-020-00644-2","article-title":"Treatment updates for neuromuscular channelopathies","volume":"22","author":"Jitpimolmard","year":"2020","journal-title":"Curr Treat Options Neurol"},{"key":"2023041916415153800_awac441-B4","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1212\/WNL.0000000000002416","article-title":"Randomized, placebo-controlled trials of dichlorphenamide in periodic paralysis","volume":"86","author":"Sansone","year":"2016","journal-title":"Neurology"},{"key":"2023041916415153800_awac441-B5","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/1531-8249(200001)47:1<46::AID-ANA9>3.0.CO;2-H","article-title":"Randomized trials of dichlorphenamide in the periodic paralyses. 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