{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T11:01:38Z","timestamp":1784372498705,"version":"3.55.0"},"reference-count":53,"publisher":"Canadian Science Publishing","issue":"9","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Appl. Physiol. Nutr. Metab."],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:p> The large conductance Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup> (BK) channels, abundantly expressed in coronary artery smooth muscle cells (SMCs), play a pivotal role in regulating coronary circulation. A large body of evidence indicates that coronary arterial BK channel function is diminished in both type 1 and type 2 diabetes. However, the consequence of coronary BK channel dysfunction in diabetes is not clear. We hypothesized that impaired coronary BK channel function exacerbates myocardial ischemia\/reperfusion (I\/R) injury in streptozotocin-induced diabetic mice. Combining patch-clamp techniques and cellular biological approaches, we found that diabetes facilitated the colocalization of angiotensin II (Ang II) type 1 receptors and BK channel \u03b1-subunits (BK-\u03b1), but not BK channel \u03b21-subunits (BK-\u03b21), in the caveolae of coronary SMCs. This caveolar compartmentation in vascular SMCs not only enhanced Ang II-mediated inhibition of BK-\u03b1 but also produced a physical disassociation between BK-\u03b1 and BK-\u03b21, leading to increased infarct size in diabetic hearts. Most importantly, genetic ablation of caveolae integrity or pharmacological activation of coronary BK channels protected the cardiac function of diabetic mice from experimental I\/R injury in both in vivo and ex vivo preparations. Our results demonstrate a vascular ionic mechanism underlying the poor outcome of myocardial injury in diabetes. Hence, activation of coronary BK channels may serve as a therapeutic target for cardiovascular complications of diabetes. <\/jats:p>","DOI":"10.1139\/apnm-2016-0048","type":"journal-article","created":{"date-parts":[[2016,5,31]],"date-time":"2016-05-31T21:44:08Z","timestamp":1464731048000},"page":"992-1001","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Coronary arterial BK channel dysfunction exacerbates ischemia\/reperfusion-induced myocardial injury in diabetic mice"],"prefix":"10.1139","volume":"41","author":[{"given":"Tong","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Soochow University, 108 Shixin Street, Soochow, Jiangsu 215006, P.R. 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