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 K(ATP) 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.
journal_name
Circ Resjournal_title
Circulation researchauthors
Miragoli M,Salvarani N,Rohr Sdoi
10.1161/CIRCRESAHA.107.160549subject
Has Abstractpub_date
2007-10-12 00:00:00pages
755-8issue
8eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.107.160549journal_volume
101pub_type
杂志文章abstract::Transient coronary occlusion (15 minutes) does not result in irreversible myocardial injury but is associated with a depression of contractile function sustained for several hours to days ("stunned myocardium"). The defect in the contractile process responsible for this phenomenon has been suggested to be causally rel...
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更新日期:2009-08-28 00:00:00
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更新日期:2005-11-11 00:00:00
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更新日期:1993-07-01 00:00:00
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更新日期:1975-06-01 00:00:00
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更新日期:1982-09-01 00:00:00
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更新日期:2009-12-04 00:00:00