{"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":1789911700832,"version":"4.0.1"},"reference-count":51,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,4,15]],"date-time":"2018-04-15T00:00:00Z","timestamp":1523750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004923","name":"AFM-T\u00e9l\u00e9thon","doi-asserted-by":"publisher","award":["18241"],"award-info":[{"award-number":["18241"]}],"id":[{"id":"10.13039\/501100004923","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","award":["1217"],"award-info":[{"award-number":["1217"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","award":["5310"],"award-info":[{"award-number":["5310"]}],"id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients suffering from type 1 hypokalaemic periodic paralysis (HypoPP1) experience attacks of muscle paralysis associated with hypokalaemia. The disease arises from missense mutations in the gene encoding the \u03b11\u00a0subunit of the dihydropyridine receptor (DHPR), a protein complex anchored in the tubular membrane of skeletal muscle fibres which controls the release of Ca<jats:sup>2+<\/jats:sup> from sarcoplasmic reticulum and also functions as a Ca<jats:sup>2+<\/jats:sup> channel. The vast majority of mutations consist of the replacement of one of the outer arginines in S4 segments of the \u03b11\u00a0subunit by neutral residues. Early studies have shown that muscle fibres from HypoPP1 patients are abnormally depolarized at rest in low K<jats:sup>+<\/jats:sup> to the point of inducing muscle inexcitability. The relationship between HypoPP1 mutations and depolarization has long remained unknown. More recent investigations conducted in the closely structurally related voltage\u2010gated Na<jats:sup>+<\/jats:sup> and K<jats:sup>+<\/jats:sup> channels have shown that comparable S4 arginine substitutions gave rise to elevated inward currents at negative potentials called gating pore currents. Experiments performed in muscle fibres from different models revealed such an inward resting current through HypoPP1 mutated Ca<jats:sup>2+<\/jats:sup> channels. In mouse fibres transfected with HypoPP1 mutated channels, the elevated resting current was found to carry H<jats:sup>+<\/jats:sup> for the R1239H arginine\u2010to\u2010histidine mutation in a S4 segment and Na<jats:sup>+<\/jats:sup> for the V876E HypoPP1 mutation, which has the peculiarity of not being located in S4 segments. Muscle paralysis probably results from the presence of a gating pore current associated with hypokalaemia for both mutations, possibly aggravated by external acidosis for the R1239H mutation.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp12917-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1113\/jp274955","type":"journal-article","created":{"date-parts":[[2018,3,24]],"date-time":"2018-03-24T01:48:23Z","timestamp":1521856103000},"page":"2019-2027","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["When muscle Ca<sup>2+<\/sup> channels carry monovalent cations through gating pores: insights into the pathophysiology of type 1 hypokalaemic periodic 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