title: Cardiac expression of skeletal muscle sodium channels increases longitudinal conduction velocity in the canine 1-week myocardial infarction.
abstract: BACKGROUND
  Skeletal muscle sodium channel (Nav1.4) expression in border zone myocardium increases action potential upstroke velocity in depolarized isolated tissue. Because resting membrane potential in the 1-week canine infarct is reduced, we hypothesized that conduction velocity (CV) is greater in Nav1.4 dogs compared with in control dogs.
  
  
  OBJECTIVE
  The purpose of this study was to measure CV in the infarct border zone border in dogs with and without Nav1.4 expression.
  
  
  METHODS
  Adenovirus was injected in the infarct border zone in 34 dogs. The adenovirus incorporated the Nav1.4- and a green fluorescent protein (GFP) gene (Nav1.4 group, n = 16) or only GFP (n = 18). After 1 week, upstroke velocity and CV were measured by sequential microelectrode recordings at 4 and 7 mM [K(+)] in superfused epicardial slabs. High-density in vivo epicardial activation mapping was performed in a subgroup (8 Nav1.4, 6 GFP) at three to four locations in the border zone. Microscopy and antibody staining confirmed GFP or Nav1.4 expression.
  
  
  RESULTS
  Infarct sizes were similar between groups (30.6% +/- 3% of left ventricle mass, mean +/- standard error of the mean). Longitudinal CV was greater in Nav1.4 than in GFP sites (58.5 +/- 1.8 vs. 53.3 +/- 1.2 cm/s, 20 and 15 sites, respectively; P <.05). Transverse CV was not different between the groups. In tissue slabs, dV/dt(max) was higher and CV was greater in Nav1.4 than in control at 7 mM [K(+)] (P <.05). Immunohistochemical Nav1.4 staining was seen at the longitudinal ends of the myocytes.
  
  
  CONCLUSIONS
  Nav1.4 channels in myocardium surviving 1 week infarction increases longitudinal but not transverse CV, consistent with the increased dV/dt(max) and with the cellular localization of Nav1.4.
authors.affiliation: Experimental Cardiology Group, Center for Heart Failure Research, Academic Medical Center, Amsterdam, The Netherlands. r.coronel@amc.nl
authors.forename: Ruben
authors.initials: R
authors.lastname: Coronel
authors.forename: David H
authors.initials: DH
authors.lastname: Lau
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Sosunov
authors.forename: Michiel J
authors.initials: MJ
authors.lastname: Janse
authors.forename: Peter
authors.initials: P
authors.lastname: Danilo
authors.forename: Evgeny P
authors.initials: EP
authors.lastname: Anyukhovsky
authors.forename: Francien J G
authors.initials: FJ
authors.lastname: Wilms-Schopman
authors.forename: Tobias
authors.initials: T
authors.lastname: Opthof
authors.forename: Iryna N
authors.initials: IN
authors.lastname: Shlapakova
authors.forename: Nazira
authors.initials: N
authors.lastname: Ozgen
authors.forename: Kevin
authors.initials: K
authors.lastname: Prestia
authors.forename: Yelena
authors.initials: Y
authors.lastname: Kryukova
authors.forename: Ira S
authors.initials: IS
authors.lastname: Cohen
authors.forename: Richard B
authors.initials: RB
authors.lastname: Robinson
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rosen
mesh_terms: D000200:Action Potentials; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D006329:Heart Conduction System / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000502:physiology*; D009203:Myocardial Infarction / Q000503:physiopathology*; D015222:Sodium Channels / Q000096:biosynthesis*
chemical_list: D015222:Sodium Channels
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