{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T21:05:57Z","timestamp":1790888757113,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T00:00:00Z","timestamp":1138752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    MinK\u2010related peptide 2 (MiRP2) and Kv3.4 subunits assemble in skeletal muscle to create subthreshold, voltage\u2010gated potassium channels. MiRP2 acts on Kv3.4 to shift the voltage dependence of activation, speed recovery from inactivation, suppress cumulative inactivation and increase unitary conductance. We previously found an R83H missense mutation in MiRP2 that segregated with periodic paralysis in two families and diminished the effects of MiRP2 on Kv3.4. Here we show that MiRP2 has a single, functional PKC phosphorylation site at serine 82 and that normal MiRP2\u2010Kv3.4 function requires phosphorylation of the site. The R83H variant does not prevent PKC phosphorylation of neighboring S82; rather, the change shifts the voltage dependence of activation and endows MiRP2\u2010Kv3.4 channels with sensitivity to changes in intracellular pH across the physiological range. Thus, current passed by single R83H channels decreases as internal pH is lowered (p\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>a<\/jats:sub>\n                    \u223c7.3, consistent with histidine protonation) whereas wild\u2010type channels are largely insensitive. These findings identify a key regulatory domain in MiRP2 and suggest a mechanistic link between acidosis and episodes of periodic paralysis.\u2014Abbott, G. W., Butler, M. H., Goldstein, S. A. N. Phosphorylation and protonation of neighboring MiRP2 sites: function and pathophysiology of MiRP2\u2010Kv3.4 potassium channels in periodic paralysis.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    20, 293\u2013301 (2006)\n                  <\/jats:p>","DOI":"10.1096\/fj.05-5070com","type":"journal-article","created":{"date-parts":[[2006,1,31]],"date-time":"2006-01-31T19:58:03Z","timestamp":1138737483000},"page":"293-301","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Phosphorylation and protonation of neighboring MiRP2 sites: function and pathophysiology of MiRP2\u2010Kv3.4 potassium channels in periodic paralysis"],"prefix":"10.1096","volume":"20","author":[{"given":"Geoffrey W.","family":"Abbott","sequence":"first","affiliation":[{"name":"Greenberg Division of Cardiology, Department of Medicine and Department of Pharmacology Cornell University, Weill Medical College  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret H.","family":"Butler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and The Institute of Molecular Pediatric Sciences University of Chicago, Pritzker School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve A. N.","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and The Institute of Molecular Pediatric Sciences University of Chicago, Pritzker School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,2]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033583599003467"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2004.06.018"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/384078a0"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/384080a0"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80728-X"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00207-0"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-002-0364-0"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.180223197"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199705293362204"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1197-338"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.12.2179"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(98)00123-5"},{"key":"e_1_2_6_14_1","first-page":"94S","article-title":"Channelopathies: ion channel disorders of muscle as a paradigm for paroxysmal disorders of the nervous system","volume":"44","author":"Ptacek L. 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