{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T02:38:17Z","timestamp":1777603097619,"version":"3.51.4"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,1,1]],"date-time":"2002-01-01T00:00:00Z","timestamp":1009843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:p>Mutations of <jats:italic>KCNA1<\/jats:italic>, which codes for the K<jats:sup>+<\/jats:sup> channel subunit hKv1.1, are associated with the human autosomal dominant disease episodic ataxia type 1 (EA1). Five recently described mutations are associated with a broad range of phenotypes: neuromyotonia alone or with seizures, EA1 with seizures, or very drug\u2010resistant EA1. Here we investigated the consequences of each mutation for channel assembly, trafficking, gating and permeation. We related data obtained from co\u2010expression of mutant and wild\u2010type hKv1.1 to the results of expressing mutant\u2010wild\u2010type fusion proteins, and combined electrophysiological recordings in <jats:italic>Xenopus<\/jats:italic> oocytes with a pharmacological discrimination of the contribution of mutant and wild\u2010type subunits to channels expressed at the membrane. We also applied confocal laser scanning microscopy to measure the level of expression of either wild\u2010type or mutant subunits tagged with green fluorescent protein (GFP). R417stop truncates most of the C\u2010terminus and is associated with severe drug\u2010resistant EA1. Electrophysiological and pharmacological measurements indicated that the mutation impairs both tetramerisation of R417stop with wild\u2010type subunits, and membrane targeting of heterotetramers. This conclusion was supported by confocal laser scanning imaging of enhanced GFP (EGFP)\u2010tagged hKv1.1 subunits. Co\u2010expression of R417stop with wild\u2010type hKv1.2 subunits yielded similar results to co\u2010expression with wild\u2010type hKv1.1. Mutations associated with typical EA1 (V404I) or with neuromyotonia alone (P244H) significantly affected neither tetramerisation nor trafficking, and only altered channel kinetics. Two other mutations associated with a severe phenotype (T226R, A242P) yielded an intermediate result. The phenotypic variability of <jats:italic>KCNA1<\/jats:italic> mutations is reflected in a wide range of disorders of channel assembly, trafficking and kinetics.<\/jats:p>","DOI":"10.1113\/jphysiol.2001.013242","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:45:57Z","timestamp":1027773957000},"page":"5-23","source":"Crossref","is-referenced-by-count":63,"title":["Variable K<sup>+<\/sup> channel subunit dysfunction in inherited mutations of <i>KCNA1<\/i>"],"prefix":"10.1113","volume":"538","author":[{"given":"Ruth","family":"Rea","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Spauschus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise H.","family":"Eunson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael G.","family":"Hanna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitri M.","family":"Kullmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,1]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90022-5"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5349.403"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00718-0"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1999.00659.x"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1094-136"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/113.5.1361"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0198-53"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0730849.x"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410400422"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.5.1200"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5360.69"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200010)48:4<647::AID-ANA12>3.0.CO;2-Q"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870010404"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90276-J"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/345530a0"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.22.14021"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90277-K"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/378085a0"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1998.00441.x"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.46.29321"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90239-A"},{"key":"e_1_2_5_23_1","first-page":"702","article-title":"A gene for episodic ataxia\/myokymia maps to chromosome 12p13","volume":"55","author":"Litt M.","year":"1994","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_5_24_1","first-page":"400","article-title":"Hereditary myokymia and paroxysmal ataxia linked to chromosome 12 is responsive to acetazolamide","volume":"59","author":"Lubbers W. 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