Myofibroblasts induce ectopic activity in cardiac tissue

Michele Miragoli, Nicolò Salvarani, Stephan Rohr

Research output: Contribution to journalArticlepeer-review

Abstract

Focal ectopic activity in cardiac tissue is a key factor in the initiation and perpetuation of tachyarrhythmias. Because myofibroblasts as present in fibrotic remodeled myocardia and infarct scars depolarize cardiomyocytes by heterocellular electrotonic interactions via gap junctions in vitro, we investigated using strands of cultured ventricular cardiomyocytes coated with myofibroblasts, whether this interaction might give rise to depolarization- induced abnormal automaticity. Whereas uncoated cardiomyocyte strands were invariably quiescent, myofibroblasts induced synchronized spontaneous activity in a density dependent manner. Activations appeared at spatial myofibroblast densities >15.7% and involved more than 80% of the preparations at myofibroblast densities of 50%. Spontaneous activity was based on depolarization-induced automaticity as evidenced by: (1) suppression of activity by the sarcolemmal KATP channel opener P-1075; (2) induction of activity in current-clamped single cardiomyocytes undergoing depolarization to potentials similar to those induced by myofibroblasts in cardiomyocyte strands; and (3) induction of spontaneous activity in cardiomyocyte strands coated with connexin 43 transfected Hela cells but not with communication deficient HeLa wild-type cells. Apart from unveiling the mechanism underlying the hallmark of monolayer cultures of cardiomyocytes, ie, spontaneous electromechanical activity, these findings open the perspective that myofibroblasts present in structurally remodeled myocardia following pressure overload and infarction might contribute to arrhythmogenesis by induction of ectopic activity.

Original languageEnglish
Pages (from-to)755-758
Number of pages4
JournalCirculation Research
Volume101
Issue number8
DOIs
Publication statusPublished - Oct 2007

Keywords

  • Arrhythmia
  • Cardiac myofibroblasts
  • Cell transplantation
  • Heart cell culture
  • Spontaneous activity

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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