Myofibroblasts Induce Ectopic Activity in Cardiac Tissue

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 in...

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Bibliographic Details
Published in:	Circulation research 2007-10, Vol.101 (8), p.755-758
Main Authors:	Miragoli, Michele, Salvarani, Nicolò, Rohr, Stephan
Format:	Article
Language:	eng
Subjects:	Animals Biological and medical sciences Cardiac dysrhythmias Cardiology. Vascular system Fibroblasts - cytology Fibroblasts - physiology Fundamental and applied biological sciences. Psychology Heart HeLa Cells Humans Medical sciences Myocardium - cytology Myocytes, Cardiac - cytology Myocytes, Cardiac - physiology Rats Ventricular Premature Complexes - physiopathology Vertebrates: cardiovascular system
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Summary:	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.
ISSN:	0009-7330 1524-4571