Cardiac expression of skeletal muscle sodium channels increases longitudinal conduction velocity in the canine 1-week myocardial infarction.
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.
Coronel
Ruben
R
Experimental Cardiology Group, Center for Heart Failure Research, Academic Medical Center, Amsterdam, The Netherlands. r.coronel@amc.nl
Lau
David H
DH
Sosunov
Eugene A
EA
Janse
Michiel J
MJ
Danilo
Peter
P
Anyukhovsky
Evgeny P
EP
Wilms-Schopman
Francien J G
FJ
Opthof
Tobias
T
Shlapakova
Iryna N
IN
Ozgen
Nazira
N
Prestia
Kevin
K
Kryukova
Yelena
Y
Cohen
Ira S
IS
Robinson
Richard B
RB
Rosen
Michael R
MR
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*
D015222:Sodium Channels
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