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Ishikawa, T.* ; Sato, A.* ; Marcou, C.A.* ; Tester, D.J.* ; Ackerman, M.J.* ; Crotti, L. ; Schwartz, P.J.* ; On, Y.K.* ; Park, J.E.* ; Nakamura, K.* ; Hiraoka, M.* ; Nakazawa, K.* ; Sakurada, H.* ; Arimura, T.* ; Makita, N.* ; Kimura, A.*

A novel disease gene for Brugada syndrome: Sarcolemmal membrane-associated protein gene mutations impair intracellular trafficking of hNav1.5.

Circ.-Arrhythmia Electrophysiol. 5, 1098-1107 (2012)
Verlagsversion DOI PMC
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Background-Mutations in genes including SCN5A encoding the a-subunit of the cardiac sodium channel (hNav1.5) cause Brugada syndrome via altered function of cardiac ion channels, but more than two-thirds of Brugada syndrome remains pathogenetically elusive. T-tubules and sarcoplasmic reticulum are essential in excitation of cardiomyocytes, and sarcolemmal membrane-associated protein (SLMAP) is a protein of unknown function localizing at T-tubules and sarcoplasmic reticulum. Methods and Results-We analyzed 190 unrelated Brugada syndrome patients for mutations in SLMAP. Two missense mutations, Val269Ile and Glu710Ala, were found in heterozygous state in 2 patients but were not found in healthy individuals. Membrane surface expression of hNav1.5 in the transfected cells was affected by the mutations, and silencing of mutant SLMAP by small interfering RNA rescued the surface expression of hNav1.5. Whole-cell patch-clamp recordings of hNav1.5-expressing cells transfected with mutant SLMAP confirmed the reduced hNav1.5 current. Conclusions-The mutations in SLMAP may cause Brugada syndrome via modulating the intracellular trafficking of hNav1.5 channel. (Circ Arrhythm Electrophysiol. 2012;5:1098-1107.)
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Arrhythmia Mechanisms ; Genes ; Ion Channels ; Sarcoplasmic Reticulum; Sudden Cardiac Death ; Polymorphic Ventricular-tachycardia ; Ryanodine Receptor Gene ; St-segment-elevation ; Long Qt Syndrome ; J-wave Syndromes ; Missense Mutation ; Channel ; Prevalence ; Cardiomyopathy
Sprache englisch
Veröffentlichungsjahr 2012
HGF-Berichtsjahr 2013
ISSN (print) / ISBN 1941-3149
e-ISSN 1941-3084
Zeitschrift Circulation: Arrhythmia and Electrophysiology
Quellenangaben Band: 5, Heft: 6, Seiten: 1098-1107 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500700-001
PubMed ID 23064965
DOI 10.1161/CIRCEP.111.969972
WOS ID WOS:000313586900017
Scopus ID 84873856880
Erfassungsdatum 2013-02-14
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