{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:16:18Z","timestamp":1791249378290,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,2,17]],"date-time":"2006-02-17T00:00:00Z","timestamp":1140134400000},"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":[[2006,3]]},"abstract":"<jats:p>Methionine\u2010directed oxidation of the human Slo1 potassium channel (hSlo1) shifts the half\u2010activation voltage by \u221230 mV and markedly slows channel deactivation at low concentrations of intracellular Ca<jats:sup>2<\/jats:sup><jats:sup>+<\/jats:sup> ([Ca<jats:sup>2<\/jats:sup><jats:sup>+<\/jats:sup>]<jats:sub>i<\/jats:sub>). We demonstrate here that the contemporaneous mutation of M536, M712 and M739 to leucine renders the channel functionally insensitive to methionine oxidation caused by the oxidant chloramine\u2010T (Ch\u2010T) without altering other functional characteristics. Coexpression with the auxiliary \u03b21 subunit fails to restore the full oxidative sensitivity to this triple mutant channel. The Ch\u2010T effect is mediated specifically by M536, M712 and M739 because even small changes in this residue combination interfere with the ability to remove the oxidant sensitivity following mutation. Replacement of M712 or M739, but not M536, with the hydrophilic residue glutamate largely mimics oxidation of the channel and essentially removes the Ch\u2010T sensitivity, suggesting that M712 and M739 may be part of a hydrophobic pocket disrupted by oxidation of non\u2010polar methionine to the more hydrophilic methionine sulfoxide. The increase in wild\u2010type hSlo1 open probability caused by methionine oxidation disappears at high [Ca<jats:sup>2<\/jats:sup><jats:sup>+<\/jats:sup>]<jats:sub>i<\/jats:sub> and biophysical modelling of the Ch\u2010T effect on steady\u2010state activation implicates a decrease in the allosteric coupling between Ca<jats:sup>2<\/jats:sup><jats:sup>+<\/jats:sup> binding and the pore. The dramatic increase in open probability at low [Ca<jats:sup>2<\/jats:sup><jats:sup>+<\/jats:sup>]<jats:sub>i<\/jats:sub> especially within the physiological voltage range suggests that oxidation of M536, M712 or M739 may enhance the Slo1 BK activity during conditions of oxidative stress, such as those associated with ischaemia\u2010reperfusion and neurodegenerative disease, or in response to metabolic cues.<\/jats:p>","DOI":"10.1113\/jphysiol.2005.101089","type":"journal-article","created":{"date-parts":[[2006,1,6]],"date-time":"2006-01-06T01:14:23Z","timestamp":1136510063000},"page":"329-348","source":"Crossref","is-referenced-by-count":53,"title":["Three methionine residues located within the regulator of conductance for K<sup>+<\/sup> (RCK) domains confer oxidative sensitivity to large\u2010conductance Ca<sup>2<\/sup><sup>+<\/sup>\u2010activated K<sup>+<\/sup> channels"],"prefix":"10.1113","volume":"571","author":[{"given":"Lindsey Ciali","family":"Santarelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramez","family":"Wassef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan H.","family":"Heinemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinori","family":"Hoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,2,17]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14660820310011278"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(03)70023-X"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(91)90045-U"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/35038011"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(00)76583-0"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.18.9932"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)01616-0"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.110.3.257"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-13-04942.1997"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1585"},{"key":"e_1_2_5_12_1","first-page":"L593","article-title":"Cigarette smoking, emphysema, and damage to alpha 1\u2010proteinase inhibitor","volume":"266","author":"Evans MD","year":"1994","journal-title":"Am J Physiol"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(98)77830-0"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1992.tb10990.x"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302034200"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00291.2005"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.20028605"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.114.2.277"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200509262"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2795(76)90179-3"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-24-09585.2001"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.278.2.C235"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/417515a"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00236-7"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1998.5627"},{"key":"e_1_2_5_26_1","doi-asserted-by":"crossref","first-page":"4022","DOI":"10.1016\/S0021-9258(18)50689-X","article-title":"The oxidative inactivation of human alpha\u20101\u2010proteinase inhibitor. 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