Referenced in: none

Automatically associated channels: Nav1.4

Title: Cardiac expression of skeletal muscle sodium channels increases longitudinal conduction velocity in the canine 1-week myocardial infarction.

Authors: Ruben Coronel, David H Lau, Eugene A Sosunov, Michiel J Janse, Peter Danilo, Evgeny P Anyukhovsky, Francien J G Wilms-Schopman, Tobias Opthof, Iryna N Shlapakova, Nazira Ozgen, Kevin Prestia, Yelena Kryukova, Ira S Cohen, Richard B Robinson, Michael R Rosen

Journal, date & volume: Heart Rhythm, 2010 Aug , 7, 1104-10

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20385252

Abstract
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.The purpose of this study was to measure CV in the infarct border zone border in dogs with and without Nav1.4 expression.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.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.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.