Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Myocytes, while giving rise to the bulk volume of normal cardiac muscle, form a "minority cell population" in the heart compared with nonmyocytes, chiefly fibroblasts. The heterogeneous cell types show very intimate spatial interrelation in situ, with virtually every myocyte in the mammalian heart bordering to 1 or more fibroblasts. Nonetheless, gap junction coupling in the heart is traditionally assumed to occur exclusively between myocytes. Yet, both freshly isolated cells and cell cultures have unambiguously shown functional heterogeneous myocyte-fibroblast coupling (mainly via connexin 43). Such coupling is sufficient, in vitro, to synchronize spontaneous beating in distant myocytes, connected over distances of up to 300 microm by fibroblasts only. More recently, functional myocyte-fibroblast coupling (via connexin 45) has been demonstrated in situ for sinoatrial node pacemaker tissue, and preliminary immunohistochemical data suggest that myocyte-fibroblast coupling may be present in postinfarct scar tissue. The functional relevance of such heterogeneous coupling for cardiac electrophysiology is only starting to emerge and has thus far mainly been assessed in theoretical studies. According to this research, fibroblasts may affect the origin and spread of excitation in several ways above and beyond formation of "passive" barriers that obstruct electrical conduction. Thus, fibroblasts may act as current sinks, contributing to the formation of unidirectional block or to the delay in atrioventricular conduction. Via short-range interaction, fibroblasts may help to smooth out propagating wave fronts, in particular in the sinoatrial node and in the cross-sheet direction of healthy ventricular myocardium, 2 tissues that might otherwise be expected to show fragmented conduction patterns. As long-distance communication lines, fibroblasts may bridge posttransplantation or ischemic scar tissue, with beneficial or detrimental effects on organ function (depending on the relation to normal conduction patterns), and explain the recruitment of myocyte islands embedded in fibrotic scar tissue. The inherent mechanosensitivity of cardiac fibroblasts could, furthermore, allow them to play a sensory role and to affect cardiac electrophysiology via mechanoelectric feedback. This article reviews the currently available experimental and theoretical evidence on the previous scenarios, and highlights areas for further research.

Original publication




Journal article


J Electrocardiol

Publication Date





45 - 50


Animals, Cell Communication, Connexins, Electric Conductivity, Fibroblasts, Gap Junctions, Humans, Myocytes, Cardiac, Sinoatrial Node