{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:03:52Z","timestamp":1790787832012,"version":"4.1.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,4,3]]},"abstract":"\n Background<\/jats:title>\n \n Two\u2010pore K\n +<\/jats:sup>\n channels have emerged as potential targets to selectively regulate cardiac cell membrane excitability; however, lack of specific inhibitors and relevant animal models has impeded the effort to understand the role of 2\u2010pore K\n +<\/jats:sup>\n channels in the heart and their potential as a therapeutic target. The objective of this study was to determine the role of mechanosensitive 2\u2010pore K\n +<\/jats:sup>\n channel family member\n TREK<\/jats:styled-content>\n \u20101 in control of cardiac excitability.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Cardiac\u2010specific\n TREK<\/jats:styled-content>\n \u20101\u2013deficient mice (\u03b1\n MHC<\/jats:styled-content>\n \u2010\n Kcnk<\/jats:italic>\n f\/f<\/jats:sup>\n ) were generated and found to have a prevalent sinoatrial phenotype characterized by bradycardia with frequent episodes of sinus pause following stress. Action potential measurements from isolated \u03b1\n MHC<\/jats:styled-content>\n \u2010\n Kcnk2<\/jats:italic>\n f\/f<\/jats:sup>\n sinoatrial node cells demonstrated decreased background K\n +<\/jats:sup>\n current and abnormal sinoatrial cell membrane excitability. To identify novel pathways for regulating\n TREK<\/jats:styled-content>\n \u20101 activity and sinoatrial node excitability, mice expressing a truncated allele of the\n TREK<\/jats:styled-content>\n \u20101\u2013associated cytoskeletal protein \u03b2\n \n IV<\/jats:sub>\n <\/jats:styled-content>\n \u2010spectrin (\n qv<\/jats:italic>\n \n 4J<\/jats:italic>\n <\/jats:sup>\n mice) were analyzed and found to display defects in cell electrophysiology as well as loss of normal\n TREK<\/jats:styled-content>\n \u20101 membrane localization. Finally, the \u03b2\n \n IV<\/jats:sub>\n <\/jats:styled-content>\n \u2010spectrin\/\n TREK<\/jats:styled-content>\n \u20101 complex was found to be downregulated in the right atrium from a canine model of sinoatrial node dysfunction and in human cardiac disease.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These findings identify a\n TREK<\/jats:styled-content>\n \u20101\u2013dependent pathway essential for normal sinoatrial node cell excitability that serves as a potential target for selectively regulating sinoatrial node cell function.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.115.002865","type":"journal-article","created":{"date-parts":[[2016,4,21]],"date-time":"2016-04-21T01:58:41Z","timestamp":1461203921000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":60,"title":["Two\u2010Pore K\n +<\/sup>\n Channel TREK\u20101 Regulates Sinoatrial Node Membrane Excitability"],"prefix":"10.1161","volume":"5","author":[{"given":"Sathya D.","family":"Unudurthi","sequence":"first","affiliation":[{"name":"The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH"},{"name":"Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangqiong","family":"Wu","sequence":"additional","affiliation":[{"name":"The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH"},{"name":"Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Qian","sequence":"additional","affiliation":[{"name":"The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH"},{"name":"Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Foued","family":"Amari","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Immunology & Medical Genetics, The Ohio State University Wexner Medical Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birce","family":"Onal","sequence":"additional","affiliation":[{"name":"The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH"},{"name":"Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH"},{"name":"Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Makara","sequence":"additional","affiliation":[{"name":"The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH"},{"name":"Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakima A.","family":"Smith","sequence":"additional","affiliation":[{"name":"The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH"},{"name":"Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jedidiah","family":"Snyder","sequence":"additional","affiliation":[{"name":"The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH"},{"name":"Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim V.","family":"Fedorov","sequence":"additional","affiliation":[{"name":"The Dorothy M. 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