{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T13:41:40Z","timestamp":1789911700128,"version":"4.0.1"},"reference-count":29,"publisher":"Rockefeller University Press","issue":"12","license":[{"start":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T00:00:00Z","timestamp":1568851200000},"content-version":"vor","delay-in-days":681,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T00:00:00Z","timestamp":1528070400000},"content-version":"vor","delay-in-days":209,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"name":"University Lyon 1"},{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007393","name":"Association Fran\u00e7aise contre les Myopathies","doi-asserted-by":"publisher","award":["18241"],"award-info":[{"award-number":["18241"]}],"id":[{"id":"10.13039\/100007393","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,12,4]]},"abstract":"<jats:p>Type 1 hypokalemic periodic paralysis (HypoPP1) is a poorly understood genetic neuromuscular disease characterized by episodic attacks of paralysis associated with low blood K+. The vast majority of HypoPP1 mutations involve the replacement of an arginine by a neutral residue in one of the S4 segments of the \u03b11 subunit of the skeletal muscle voltage-gated Ca2+ channel, which is thought to generate a pathogenic gating pore current. The V876E HypoPP1 mutation has the peculiarity of being located in the S3 segment of domain III, rather than an S4 segment, raising the question of whether such a mutation induces a gating pore current. Here we successfully transfer cDNAs encoding GFP-tagged human wild-type (WT) and V876E HypoPP1 mutant \u03b11 subunits into mouse muscles by electroporation. The expression profile of these WT and V876E channels shows a regular striated pattern, indicative of their localization in the t-tubule membrane. In addition, L-type Ca2+ current properties are the same in V876E and WT fibers. However, in the presence of an external solution containing low-Cl\u2212 and lacking Na+ and K+, V876E fibers display an elevated leak current at negative voltages that is increased by external acidification to a higher extent in V876E fibers, suggesting that the leak current is carried by H+ ions. However, in the presence of Tyrode\u2019s solution, the rate of change in intracellular pH produced by external acidification was not significantly different in V876E and WT fibers. Simultaneous measurement of intracellular Na+ and current in response to Na+ readmission in the external solution reveals a rate of Na+ influx associated with an inward current, which are both significantly larger in V876E fibers. These data suggest that the V876E mutation generates a gating pore current that carries strong resting Na+ inward currents in physiological conditions that are likely responsible for the severe HypoPP1 symptoms associated with this mutation.<\/jats:p>","DOI":"10.1085\/jgp.201711834","type":"journal-article","created":{"date-parts":[[2017,11,7]],"date-time":"2017-11-07T14:25:17Z","timestamp":1510064717000},"page":"1139-1148","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["Na leak with gating pore properties in hypokalemic periodic paralysis V876E mutant muscle Ca channel"],"prefix":"10.1085","volume":"149","author":[{"given":"Clarisse","family":"Fuster","sequence":"first","affiliation":[{"name":"Institut NeuroMyoGene, Universit\u00e9 Lyon 1, Universit\u00e9 de Lyon, UMR Centre National de la Recherche Scientifique 5310, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U1217, Villeurbanne, France 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimmy","family":"Perrot","sequence":"additional","affiliation":[{"name":"Institut NeuroMyoGene, Universit\u00e9 Lyon 1, Universit\u00e9 de Lyon, UMR Centre National de la Recherche Scientifique 5310, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U1217, Villeurbanne, France 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9608-643X","authenticated-orcid":true,"given":"Christine","family":"Berthier","sequence":"additional","affiliation":[{"name":"Institut NeuroMyoGene, Universit\u00e9 Lyon 1, Universit\u00e9 de Lyon, UMR Centre National de la Recherche Scientifique 5310, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U1217, Villeurbanne, France 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Jacquemond","sequence":"additional","affiliation":[{"name":"Institut NeuroMyoGene, Universit\u00e9 Lyon 1, Universit\u00e9 de Lyon, UMR Centre National de la Recherche Scientifique 5310, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U1217, Villeurbanne, France 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Charnet","sequence":"additional","affiliation":[{"name":"Institut des Biomol\u00e9cules Max Mousseron, Universit\u00e9 Montpellier 1 et 2, UMR Centre National de la Recherche Scientifique 5247, Montpellier, France 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7131-7828","authenticated-orcid":true,"given":"Bruno","family":"Allard","sequence":"additional","affiliation":[{"name":"Institut NeuroMyoGene, Universit\u00e9 Lyon 1, Universit\u00e9 de Lyon, UMR Centre National de la Recherche Scientifique 5310, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U1217, Villeurbanne, France 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2017,11,7]]},"reference":[{"key":"2023072623562796200_bib1","doi-asserted-by":"publisher","first-page":"7904","DOI":"10.1073\/pnas.0702638104","article-title":"Two atomic constraints unambiguously position the S4 segment relative to S1 and S2 segments in the closed state of Shaker K channel","volume":"104","author":"Campos","year":"2007","journal-title":"Proc. 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