{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T20:44:00Z","timestamp":1781988240980,"version":"3.54.5"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,1,3]],"date-time":"2018-01-03T00:00:00Z","timestamp":1514937600000},"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","award":["HL126905"],"award-info":[{"award-number":["HL126905"]}],"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":[[2018,3]]},"abstract":"<jats:p>\n                    ATP\u2010sensitive K\n                    <jats:sup>+<\/jats:sup>\n                    (K\n                    <jats:sub>ATP<\/jats:sub>\n                    ) channels uniquely link cellular energy metabolism to membrane excitability and are ex\u03c1ressed in diverse cell ty\u03c1es that range from the endocrine pancreas to neurons and smooth, skeletal, and cardiac muscle. A decrease in the surface ex\u03c1ression of K\n                    <jats:sub>ATP<\/jats:sub>\n                    channels has been linked to various disorders, including dysregulated insulin secretion, abnormal blood pressure, and impaired resistance to cardiac injury. In contrast, up\u2010regulation of K\n                    <jats:sub>ATP<\/jats:sub>\n                    channel surface expression may be protective, for example, by mediating the beneficial effect of ischemic preconditioning. Molecular mechanisms that regulate K\n                    <jats:sub>ATP<\/jats:sub>\n                    channel trafficking are poorly understood. Here, we used cellular assays with immunofluorescence, surface biotinylation, and \u03c1atch clamping to demonstrate that Eps15 homology domain\u2010containing protein 2 (EHD2) is a novel positive regulator of K\n                    <jats:sub>ATP<\/jats:sub>\n                    channel trafficking to increase surface K\n                    <jats:sub>ATP<\/jats:sub>\n                    channel density. EHD2 had no effect on cardiac Na\n                    <jats:sup>+<\/jats:sup>\n                    channels (Nav1.5). The effect is specific to EHD2 as other members of the EHD family\u2014EHD1, EHD3, and EHD4\u2014had no effect on K\n                    <jats:sub>ATP<\/jats:sub>\n                    channel surface expression. EHD2 did not directly affect K\n                    <jats:sub>ATP<\/jats:sub>\n                    channel properties as unitary conductance and ATP sensitivity were unchanged. Instead, we observed that the mechanism by which EHD2 increases surface expression is by stabilizing K\n                    <jats:sub>ATP<\/jats:sub>\n                    channel\u2010\n                    <jats:bold>\n                      containing caveolar structures, which results in a reduced rate of endocytosis. EHD2 also regulated K\n                      <jats:sub>ATP<\/jats:sub>\n                      channel trafficking in isolated cardiomyocytes, which validated the physiologic relevance of these observations. Pathophysiologically, EHD2 may be car\u2010 dioprotective as a dominant\u2010negative EHD2 mutant sensitized cardiomyocytes to ischemic damage. Our find\u2010 ings highlight EHD2 as a potential pharmacologic target in the treatment of diseases with K\n                      <jats:sub>ATP<\/jats:sub>\n                      channel trafficking defects.\n                    <\/jats:bold>\n                    \u2014\n                    <jats:bold>\n                      Yang, H. Q., Jana, K., Rindler, M. J., Coetzee, W. A. The trafficking protein, EHD2, positively regulates cardiac sarcolemmal K\n                      <jats:sub>ATP<\/jats:sub>\n                      channel surface expression: role in cardioprotection. FASEB J. 32,1613\n                    <\/jats:bold>\n                    \u20101625 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700027r","type":"journal-article","created":{"date-parts":[[2017,11,13]],"date-time":"2017-11-13T15:55:13Z","timestamp":1510588513000},"page":"1613-1625","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The trafficking protein, EHD2, positively regulates cardiac sarcolemmal K\n                    <sub>ATP<\/sub>\n                    channel surface expression: role in cardioprotection"],"prefix":"10.1096","volume":"32","author":[{"given":"Hua Qian","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pediatrics New York University School of Medicine New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kundan","family":"Jana","sequence":"additional","affiliation":[{"name":"Department of Pediatrics New York University School of Medicine New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Rindler","sequence":"additional","affiliation":[{"name":"Department of Cell Biology New York University School of Medicine New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Coetzee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics New York University School of Medicine New York New York USA"},{"name":"Department of Physiology and Neuroscience New York University School of Medicine New York New York USA"},{"name":"Department of Biochemistry and Molecular Pharmacology New York University School of Medicine New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04711"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00003.2015"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00158.2016"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.212315199"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-176669"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201200324"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/35078543"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e05-05-0466"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.037051"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-8-3"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307702200"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06173"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20111010"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.216713"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.646893"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80708-4"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00857.2010"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2011.06.015"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.135.4.913"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp039"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.98"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e11-09-0787"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001640"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.75.3.576"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1315"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00256-3"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601275"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2011.01227.x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.066902"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.429548"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1216351110"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01168"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1242\/bio.016642"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.01-06-0317"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M409340200"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.084319"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1289-11.2011"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000148634.47095.ab"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.108.110817"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi049970f"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2004-0443"}],"container-title":["The 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