Effect of skeletal muscle Na(+) channel delivered via a cell platform on cardiac conduction and arrhythmia induction

Circ Arrhythm Electrophysiol. 2012 Aug 1;5(4):831-40. doi: 10.1161/CIRCEP.111.969907. Epub 2012 Jun 21.


Background: In depolarized myocardial infarct epicardial border zones, the cardiac sodium channel is largely inactivated, contributing to slow conduction and reentry. We have demonstrated that adenoviral delivery of the skeletal muscle Na(+) channel (SkM1) to epicardial border zones normalizes conduction and reduces induction of ventricular tachycardia/ventricular fibrillation. We now studied the impact of canine mesenchymal stem cells (cMSCs) in delivering SkM1.

Methods and results: cMSCs were isolated and transfected with SkM1. Coculture experiments showed cMSC/SkM1 but not cMSC alone and maintained fast conduction at depolarized potentials. We studied 3 groups in the canine 7d infarct: sham, cMSC, and cMSC/SkM1. In vivo epicardial border zones electrograms were broad and fragmented in sham, narrower in cMSCs, and narrow and unfragmented in cMSC/SkM1 (P<0.05). During programmed electrical stimulation of epicardial border zones, QRS duration in cMSC/SkM1 was shorter than in cMSC and sham (P<0.05). Programmed electrical stimulation-induced ventricular tachycardia/ventricular fibrillation was equivalent in all groups (P>0.05).

Conclusion: cMSCs provide efficient delivery of SkM1 current. The interventions performed (cMSCs or cMSC/SkM1) were neither antiarrhythmic nor proarrhythmic. Comparing outcomes with cMSC/SkM1 and viral gene delivery highlights the criticality of the delivery platform to SkM1 antiarrhythmic efficacy.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Animals, Newborn
  • Cardiac Pacing, Artificial
  • Cells, Cultured
  • Coculture Techniques
  • Disease Models, Animal
  • Dogs
  • Electrophysiologic Techniques, Cardiac
  • Humans
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / metabolism*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Myocardial Infarction / complications
  • Myocardial Infarction / genetics
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / surgery*
  • Myocytes, Cardiac / metabolism*
  • NAV1.5 Voltage-Gated Sodium Channel
  • Rats
  • Rats, Sprague-Dawley
  • Sodium / metabolism*
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Tachycardia, Ventricular / etiology
  • Tachycardia, Ventricular / genetics
  • Tachycardia, Ventricular / metabolism
  • Tachycardia, Ventricular / physiopathology
  • Tachycardia, Ventricular / prevention & control*
  • Time Factors
  • Transfection
  • Ventricular Fibrillation / etiology
  • Ventricular Fibrillation / genetics
  • Ventricular Fibrillation / metabolism
  • Ventricular Fibrillation / physiopathology
  • Ventricular Fibrillation / prevention & control*


  • Muscle Proteins
  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human
  • Scn4a protein, rat
  • Scn5a protein, rat
  • Sodium Channels
  • Sodium