title: Optical mapping of ventricular arrhythmias in LQTS mice with SCN5A mutation N1325S.
abstract: Transgenic expression of SCN5A mutation N1325S creates a mouse model for type-3 long QT syndrome (LQT3), TG-NS/LQT3. Optical mapping is a high temporal and spatial resolution fluorescence mapping system that records 256 action potentials simultaneously in a Langendorff-perfused heart. Here for the first-time, we provide a spatial view of VT in a genetic LQT3 model using optical mapping. Spontaneous VT was detected in TG-NS/LQT3 hearts, but not in littermate control hearts. VT was initiated primarily by activation of a new firing focus as well as functional conduction block of new activation waves. New firing was initiated at many different Loci in the heart, suggesting that "increased automaticity" is a key mechanism for initiation of VT. The sustained VT was maintained by a reentry mechanism. Nifedipine, an L-type calcium channel blocker, decreased the frequency of VT, indicating the involvement of abnormalities of the calcium homeostasis in the genesis of VT in TG-NS/LQT3 mice.
authors.affiliation: Department of Molecular Cardiology, Lerner Research Institute and Center for Cardiovascular Genetics, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Tian
authors.forename: Yuanna
authors.initials: Y
authors.lastname: Cheng
authors.forename: Teng
authors.initials: T
authors.lastname: Zhang
authors.forename: Mei-Ling Chang
authors.initials: ML
authors.lastname: Liao
authors.forename: Sandro L
authors.initials: SL
authors.lastname: Yong
authors.forename: Qing K
authors.initials: QK
authors.lastname: Wang
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D001216:Asparagine / Q000235:genetics / Q000378:metabolism; D005117:Cardiac Complexes, Premature / Q000235:genetics / Q000378:metabolism; D008133:Long QT Syndrome / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008801:Mexiletine / Q000627:therapeutic use; D051379:Mice; D009154:Mutation / Q000235:genetics; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009543:Nifedipine / Q000627:therapeutic use; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568321:Scn5a protein, mouse; D015222:Sodium Channels; D008801:Mexiletine; D012694:Serine; D001216:Asparagine; D009543:Nifedipine