{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:13:21Z","timestamp":1787987601335,"version":"build-2784847793"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2019,9,10]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Polycystin-1 (PC1) is a transmembrane protein originally identified in autosomal dominant polycystic kidney disease where it regulates the calcium-permeant cation channel polycystin-2. Autosomal dominant polycystic kidney disease patients develop renal failure, hypertension, left ventricular hypertrophy, and diastolic dysfunction, among other cardiovascular disorders. These individuals harbor PC1 loss-of-function mutations in their cardiomyocytes, but the functional consequences are unknown. PC1 is ubiquitously expressed, and its experimental ablation in cardiomyocyte-specific knockout mice reduces contractile function. Here, we set out to determine the pathophysiological role of PC1 in cardiomyocytes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              Wild-type and cardiomyocyte-specific PC1 knockout mice were analyzed by echocardiography. Excitation-contraction coupling was assessed in isolated cardiomyocytes and human embryonic stem cell-derived cardiomyocytes, and functional consequences were explored in heterologous expression systems. Protein-protein interactions were analyzed biochemically and by means of\n              <jats:italic>ab initio<\/jats:italic>\n              calculations.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              PC1 ablation reduced action potential duration in cardiomyocytes, decreased Ca\n              <jats:sup>2+<\/jats:sup>\n              transients, and myocyte contractility. PC1-deficient cardiomyocytes manifested a reduction in sarcoendoplasmic reticulum Ca\n              <jats:sup>2+<\/jats:sup>\n              stores attributable to a reduced action potential duration and sarcoendoplasmic reticulum Ca\n              <jats:sup>2+<\/jats:sup>\n              ATPase (SERCA) activity. An increase in outward K\n              <jats:sup>+<\/jats:sup>\n              currents decreased action potential duration in cardiomyocytes lacking PC1. Overexpression of full-length PC1 in HEK293 cells significantly reduced the current density of heterologously expressed Kv4.3, Kv1.5 and Kv2.1 potassium channels. PC1 C terminus inhibited Kv4.3 currents to the same degree as full-length PC1. Additionally, PC1 coimmunoprecipitated with Kv4.3, and a modeled PC1 C-terminal structure suggested the existence of 2 docking sites for PC1 within the N terminus of Kv4.3, supporting a physical interaction. Finally, a naturally occurring human mutant PC1\n              <jats:sup>R4228X<\/jats:sup>\n              manifested no suppressive effects on Kv4.3 channel activity.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Our findings uncover a role for PC1 in regulating multiple Kv channels, governing membrane repolarization and alterations in SERCA activity that reduce cardiomyocyte contractility.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.118.034731","type":"journal-article","created":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T09:00:16Z","timestamp":1561107616000},"page":"921-936","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Polycystin-1 Assembles With Kv Channels to Govern Cardiomyocyte Repolarization and Contractility"],"prefix":"10.1161","volume":"140","author":[{"given":"Francisco","family":"Altamirano","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Cardiology Division (F.A., G.G.S., K.M.F., S.Y.K., S.K., E.V., D.T., J.W.S., S.L., T.G.G., J.A.H.), University of Texas Southwestern Medical Center, Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele G.","family":"Schiattarella","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiology Division (F.A., G.G.S., K.M.F., S.Y.K., S.K., E.V., D.T., J.W.S., S.L., T.G.G., J.A.H.), University of Texas Southwestern Medical Center, Dallas."},{"name":"Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy (G.G.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin M.","family":"French","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiology Division (F.A., G.G.S., K.M.F., S.Y.K., S.K., E.V., D.T., J.W.S., S.L., T.G.G., J.A.H.), University of Texas Southwestern Medical Center, Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiology Division (F.A., G.G.S., K.M.F., S.Y.K., S.K., E.V., D.T., J.W.S., S.L., T.G.G., J.A.H.), University of Texas Southwestern Medical Center, Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Engelberger","sequence":"additional","affiliation":[{"name":"Institute for Biological and Medical Engineering, Schools of Engineering, Medicine, and Biological Sciences, Pontificia Universidad Catolica de Chile, Santiago, Chile (F.E., C.A.R.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergii","family":"Kyrychenko","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiology Division (F.A., G.G.S., K.M.F., S.Y.K., S.K., E.V., D.T., J.W.S., S.L., T.G.G., J.A.H.), University of Texas Southwestern Medical Center, Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Villalobos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiology Division (F.A., G.G.S., K.M.F., S.Y.K., S.K., E.V., D.T., J.W.S., S.L., T.G.G., J.A.H.), University of Texas Southwestern Medical Center, Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiology Division (F.A., G.G.S., K.M.F., S.Y.K., S.K., E.V., D.T., J.W.S., S.L., T.G.G., J.A.H.), University of Texas Southwestern Medical Center, Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay W.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiology Division (F.A., G.G.S., K.M.F., S.Y.K., S.K., E.V., D.T., J.W.S., S.L., T.G.G., J.A.H.), University of Texas Southwestern Medical Center, Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar A.","family":"Ramirez-Sarmiento","sequence":"additional","affiliation":[{"name":"Institute for Biological and Medical Engineering, Schools of Engineering, Medicine, and Biological Sciences, Pontificia Universidad Catolica de Chile, Santiago, Chile (F.E., C.A.R.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Lavandero","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiology Division (F.A., G.G.S., K.M.F., S.Y.K., S.K., E.V., D.T., J.W.S., S.L., T.G.G., J.A.H.), University of Texas Southwestern Medical Center, Dallas."},{"name":"Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, Chile (S.L.)."},{"name":"Corporaci\u00f3n Centro de Estudios Cient\u00edficos de las Enfermedades Cr\u00f3nicas (CECEC), Santiago, Chile (S.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Gillette","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiology Division (F.A., G.G.S., K.M.F., S.Y.K., S.K., E.V., D.T., J.W.S., S.L., T.G.G., J.A.H.), University of Texas Southwestern Medical Center, Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiology Division (F.A., G.G.S., K.M.F., S.Y.K., S.K., E.V., D.T., J.W.S., S.L., T.G.G., J.A.H.), University of Texas Southwestern Medical Center, Dallas."},{"name":"Department of Molecular Biology (J.A.H.), University of Texas Southwestern Medical Center, 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