{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:25:51Z","timestamp":1790965551286,"version":"4.1.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>\n              Defects of cytoarchitectural proteins can cause left ventricular noncompaction, which is often associated with conduction system diseases. We have previously identified a p.D117N mutation in the LIM domain-binding protein 3\u2013encoding Z-band alternatively spliced PDZ motif gene (ZASP) in a patient with left ventricular noncompaction and conduction disturbances. We sought to investigate the role of p.D117N mutation in the\n              <jats:italic>LBD3<\/jats:italic>\n              NM_001080114.1 isoform (ZASP1-D117N) for the regulation of cardiac sodium channel (Na\n              <jats:sub>v<\/jats:sub>\n              1.5) that plays an important role in the cardiac conduction system.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Effects of ZASP1-wild-type and ZASP1-D117N on Na\n              <jats:sub>v<\/jats:sub>\n              1.5 were studied in human embryonic kidney-293 cells and neonatal rat cardiomyocytes. Patch-clamp study demonstrated that ZASP1-D117N significantly attenuated\n              <jats:italic>I<\/jats:italic>\n              <jats:sub>Na<\/jats:sub>\n              by 27% in human embryonic kidney-293 cells and by 32% in neonatal rat cardiomyocytes. In addition, ZASP1-D117N rightward shifted the voltage-dependent activation and inactivation in both systems. In silico simulation using Luo-Rudy phase 1 model demonstrated that altered Na\n              <jats:sub>v<\/jats:sub>\n              1.5 function can reduce cardiac conduction velocity by 28% compared with control. Pull-down assays showed that both wild-type and ZASP1-D117N can complex with Na\n              <jats:sub>v<\/jats:sub>\n              1.5 and telethonin\/T-Cap, which required intact PDZ domains. Immunohistochemical staining in neonatal rat cardiomyocytes demonstrates that ZASP1-D117N did not significantly disturb the Z-line structure. Disruption of cytoskeletal networks with 5-iodonaphthalene-1-sulfonyl homopiperazine and cytochalasin D abolished the effects of ZASP1-D117N on Na\n              <jats:sub>v<\/jats:sub>\n              1.5.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              ZASP1 can form protein complex with telethonin\/T-Cap and Na\n              <jats:sub>v<\/jats:sub>\n              1.5. The left ventricular noncompaction-specific ZASP1 mutation can cause loss of function of Na\n              <jats:sub>v<\/jats:sub>\n              1.5, without significant alteration of the cytoskeletal protein complex. Our study suggests that electric remodeling can occur in left ventricular noncompaction subject because of a direct effect of mutant ZASP on Na\n              <jats:sub>v<\/jats:sub>\n              1.5.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circep.111.969220","type":"journal-article","created":{"date-parts":[[2012,8,29]],"date-time":"2012-08-29T02:41:06Z","timestamp":1346208066000},"page":"1017-1026","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":41,"title":["Loss of Function of hNa\n            <sub>v<\/sub>\n            1.5 by a ZASP1 Mutation Associated With Intraventricular Conduction Disturbances in Left Ventricular Noncompaction"],"prefix":"10.1161","volume":"5","author":[{"given":"Yutao","family":"Xi","sequence":"first","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital (Y.X., G.W., J.C.), Houston, TX; Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi\u2019an Jiaotong University (Y.X.), Xi\u2019an, China; Krannert Institute of Cardiology, Indiana University School of Medicine (T.A., I.T.), Indianapolis, IN; Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California Los Angeles (E.D.L., J.N.W., Z.Q.), Los Angeles, CA;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Ai","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital (Y.X., G.W., J.C.), Houston, TX; Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi\u2019an Jiaotong University (Y.X.), Xi\u2019an, China; Krannert Institute of Cardiology, Indiana University School of Medicine (T.A., I.T.), Indianapolis, IN; Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California Los Angeles (E.D.L., J.N.W., Z.Q.), Los Angeles, CA;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enno","family":"De Lange","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital (Y.X., G.W., J.C.), Houston, TX; Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi\u2019an Jiaotong University (Y.X.), Xi\u2019an, China; Krannert Institute of Cardiology, Indiana University School of Medicine (T.A., I.T.), Indianapolis, IN; Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California Los Angeles (E.D.L., J.N.W., Z.Q.), Los Angeles, CA;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Li","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital (Y.X., G.W., J.C.), Houston, TX; Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi\u2019an Jiaotong University (Y.X.), Xi\u2019an, China; Krannert Institute of Cardiology, Indiana University School of Medicine (T.A., I.T.), Indianapolis, IN; Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California Los Angeles (E.D.L., J.N.W., Z.Q.), Los Angeles, CA;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geru","family":"Wu","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital (Y.X., G.W., J.C.), Houston, TX; Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi\u2019an Jiaotong University (Y.X.), Xi\u2019an, China; Krannert Institute of Cardiology, Indiana University School of Medicine (T.A., I.T.), Indianapolis, IN; Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California Los Angeles (E.D.L., J.N.W., Z.Q.), Los Angeles, CA;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Brunelli","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital (Y.X., G.W., J.C.), Houston, TX; Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi\u2019an Jiaotong University (Y.X.), Xi\u2019an, China; Krannert Institute of Cardiology, Indiana University School of Medicine (T.A., I.T.), Indianapolis, IN; Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California Los Angeles (E.D.L., J.N.W., Z.Q.), Los Angeles, CA;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Buck","family":"Kyle","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital (Y.X., G.W., J.C.), Houston, TX; Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi\u2019an Jiaotong University (Y.X.), Xi\u2019an, China; Krannert Institute of Cardiology, Indiana University School of Medicine (T.A., I.T.), Indianapolis, IN; Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California Los Angeles (E.D.L., J.N.W., Z.Q.), Los Angeles, CA;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isik","family":"Turker","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital (Y.X., G.W., J.C.), Houston, TX; Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi\u2019an Jiaotong University (Y.X.), Xi\u2019an, China; Krannert Institute of Cardiology, Indiana University School of Medicine (T.A., I.T.), Indianapolis, IN; Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California Los Angeles (E.D.L., J.N.W., Z.Q.), Los Angeles, CA;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Cheng","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital (Y.X., G.W., J.C.), Houston, TX; Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi\u2019an Jiaotong University (Y.X.), Xi\u2019an, China; Krannert Institute of Cardiology, Indiana University School of Medicine (T.A., I.T.), Indianapolis, IN; Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California Los Angeles (E.D.L., J.N.W., Z.Q.), Los Angeles, CA;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Ackerman","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital (Y.X., G.W., J.C.), Houston, TX; Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi\u2019an Jiaotong University (Y.X.), Xi\u2019an, China; Krannert Institute of Cardiology, Indiana University School of Medicine (T.A., I.T.), Indianapolis, IN; Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California Los Angeles (E.D.L., J.N.W., Z.Q.), Los Angeles, CA;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinori","family":"Kimura","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital (Y.X., G.W., J.C.), Houston, TX; Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi\u2019an Jiaotong University (Y.X.), Xi\u2019an, China; Krannert Institute of Cardiology, Indiana University School of Medicine (T.A., I.T.), Indianapolis, IN; Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California Los Angeles (E.D.L., J.N.W., Z.Q.), Los Angeles, CA;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James N.","family":"Weiss","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital (Y.X., G.W., J.C.), Houston, TX; Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi\u2019an Jiaotong University (Y.X.), Xi\u2019an, China; Krannert Institute of Cardiology, Indiana University School of Medicine (T.A., I.T.), Indianapolis, IN; Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California Los Angeles (E.D.L., J.N.W., Z.Q.), Los Angeles, CA;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilin","family":"Qu","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital (Y.X., G.W., J.C.), Houston, TX; Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi\u2019an Jiaotong University (Y.X.), Xi\u2019an, China; Krannert Institute of Cardiology, Indiana University School of Medicine (T.A., I.T.), Indianapolis, IN; Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California Los Angeles (E.D.L., J.N.W., Z.Q.), Los Angeles, CA;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey J.","family":"Kim","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital (Y.X., G.W., J.C.), Houston, TX; Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi\u2019an Jiaotong University (Y.X.), Xi\u2019an, China; Krannert Institute of Cardiology, Indiana University School of Medicine (T.A., I.T.), Indianapolis, IN; Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California Los Angeles (E.D.L., J.N.W., Z.Q.), Los Angeles, CA;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgine","family":"Faulkner","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital (Y.X., G.W., J.C.), Houston, TX; Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi\u2019an Jiaotong University (Y.X.), Xi\u2019an, China; Krannert Institute of Cardiology, Indiana University School of Medicine (T.A., I.T.), Indianapolis, IN; Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California Los Angeles (E.D.L., J.N.W., Z.Q.), Los Angeles, CA;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Vatta","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital (Y.X., G.W., J.C.), Houston, TX; Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi\u2019an Jiaotong University (Y.X.), Xi\u2019an, China; Krannert Institute of Cardiology, Indiana University School of Medicine (T.A., I.T.), Indianapolis, IN; Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California Los Angeles (E.D.L., J.N.W., Z.Q.), Los Angeles, CA;..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2003.10.021"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.146.2.465"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2005.12.036"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200107092"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn400"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2007.07.019"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.107.703330"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801294105"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.635268"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circep.108.769224"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.68.6.1501"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.81.5.727"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/35059090"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0995fje"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30804"},{"issue":"1","key":"e_1_3_3_17_2","first-page":"H203","article-title":"Cytoskeleton modulates gating of voltage-dependent sodium channel in heart.","volume":"269","author":"Undrovinas AI","year":"1995","unstructured":"Undrovinas AI, Shander GS, Makielski JC. 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