Acute slowing of cardiac conduction in response to myofibroblast coupling to cardiomyocytes through N-cadherin

Susan A. Thompson, Adriana Blazeski, Craig R. Copeland, Daniel M. Cohen, Christopher S. Chen, Daniel M. Reich, Leslie Tung

Research output: Contribution to journalArticlepeer-review

Abstract

The electrophysiological consequences of cardiomyocyte and myofibroblast interactions remain unclear, and the contribution of mechanical coupling between these two cell types is still poorly understood. In this study, we examined the time course and mechanisms by which addition of myofibroblasts activated by transforming growth factor-beta (TGF-β) influence the conduction velocity (CV) of neonatal rat ventricular cell monolayers. We observed that myofibroblasts affected CV within 30. min of contact and that these effects were temporally correlated with membrane deformation of cardiomyocytes by the myofibroblasts. Expression of dominant negative RhoA in the myofibroblasts impaired both myofibroblast contraction and myofibroblast-induced slowing of cardiac conduction, whereas overexpression of constitutive RhoA had little effect. To determine the importance of mechanical coupling between these cell types, we examined the expression of the two primary cadherins in the heart (N- and OB-cadherin) at cell-cell contacts formed between myofibroblasts and cardiomyocytes. Although OB-cadherin was frequently found at myofibroblast-myofibroblast contacts, very little expression was observed at myofibroblast-cardiomyocyte contacts. The myofibroblast-induced slowing of cardiac conduction was not prevented by silencing of OB-cadherin in the myofibroblasts, and could be reversed by inhibitors of mechanosensitive channels (gadolinium or streptomycin) and cellular contraction (blebbistatin). In contrast, N-cadherin expression was commonly observed at myofibroblast-cardiomyocyte contacts, and silencing of N-cadherin in myofibroblasts prevented the myofibroblast-dependent slowing of cardiac conduction. We propose that myofibroblasts can impair the electrophysiological function of cardiac tissue through the application of contractile force to the cardiomyocyte membrane via N-cadherin junctions.

Original languageEnglish (US)
Pages (from-to)29-37
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume68
DOIs
StatePublished - Mar 2014

Keywords

  • Cadherin
  • Cardiomyocyte
  • Electrophysiology
  • Mechanobiology
  • Myofibroblast
  • Optical mapping

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Acute slowing of cardiac conduction in response to myofibroblast coupling to cardiomyocytes through N-cadherin'. Together they form a unique fingerprint.

Cite this