{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:07:37Z","timestamp":1790230057919,"version":"4.1.0"},"reference-count":51,"publisher":"American Physiological Society","issue":"9","funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["R00HL102056"],"award-info":[{"award-number":["R00HL102056"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"HHS | NIH | National Center for Research Resources (NCRR)","doi-asserted-by":"publisher","award":["S10RR027535"],"award-info":[{"award-number":["S10RR027535"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2016,5,1]]},"abstract":"<jats:p> Activation of vascular endothelial small- (K<jats:sub>Ca<\/jats:sub>2.3, SK3) or intermediate- (K<jats:sub>Ca<\/jats:sub>3.1, IK1) conductance Ca<jats:sup>2+<\/jats:sup>-activated potassium channels induces vasorelaxation via an endothelium-derived hyperpolarization (EDH) pathway. Although the activation of SK3 and IK1 channels converges on EDH, their subcellular effects on signal transduction are different and not completely clear. In this study, a novel endothelium-specific SK3 knockout (SK3<jats:sup>\u2212\/\u2212<\/jats:sup>) mouse model was utilized to specifically examine the contribution of SK3 channels to mesenteric artery vasorelaxation, endothelial Ca<jats:sup>2+<\/jats:sup> dynamics, and blood pressure. The absence of SK3 expression was confirmed using real-time quantitative PCR and Western blot analysis. Functional studies showed impaired EDH-mediated vasorelaxation in SK3<jats:sup>\u2212\/\u2212<\/jats:sup> small mesenteric arteries. Immunostaining results from SK3<jats:sup>\u2212\/\u2212<\/jats:sup> vessels confirmed the absence of SK3 and further showed altered distribution of transient receptor potential channels, type 4 (TRPV4). Electrophysiological recordings showed a lack of SK3 channel activity, while TRPV4-IK1 channel coupling remained intact in SK3<jats:sup>\u2212\/\u2212<\/jats:sup> endothelial cells. Moreover, Ca<jats:sup>2+<\/jats:sup> imaging studies in SK3<jats:sup>\u2212\/\u2212<\/jats:sup> endothelium showed increased Ca<jats:sup>2+<\/jats:sup> transients with reduced amplitude and duration under basal conditions. Importantly, SK3<jats:sup>\u2212\/\u2212<\/jats:sup> endothelium lacked a distinct type of Ca<jats:sup>2+<\/jats:sup> dynamic that is sensitive to TRPV4 activation. Blood pressure measurements showed that the SK3<jats:sup>\u2212\/\u2212<\/jats:sup> mice were hypertensive, and the blood pressure increase was further enhanced during the 12-h dark cycle when animals are most active. Taken together, our results reveal a previously unappreciated SK3 signaling microdomain that modulates endothelial Ca<jats:sup>2+<\/jats:sup> dynamics, vascular tone, and blood pressure. <\/jats:p>","DOI":"10.1152\/ajpheart.00787.2015","type":"journal-article","created":{"date-parts":[[2016,3,4]],"date-time":"2016-03-04T22:39:51Z","timestamp":1457131191000},"page":"H1151-H1163","source":"Crossref","is-referenced-by-count":29,"title":["Endothelial SK3 channel-associated Ca<sup>2+<\/sup> microdomains modulate blood pressure"],"prefix":"10.1152","volume":"310","author":[{"given":"Fui C.","family":"Yap","sequence":"first","affiliation":[{"name":"Department of Physiology and Cell Biology, University of South Alabama, Mobile, Alabama;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, University of South Alabama, Mobile, 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