Fibroblast–myocyte electrotonic coupling: Does it occur in native cardiac tissue?

Abstract

Heterocellular electrotonic coupling between cardiac myocytes and non-excitable connective tissue cells has been a long-established and well-researched fact in vitro. Whether or not such coupling exists in vivo has been a matter of considerable debate. This paper reviews the development of experimental insight and conceptual views on this topic, describes evidence in favour of and against the presence of such coupling in native myocardium, and identifies directions for further study needed to resolve the riddle, perhaps less so in terms of principal presence which has been demonstrated, but undoubtedly in terms of extent, regulation, patho-physiological context, and actual relevance of cardiac myocyte–non-myocyte coupling in vivo. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium."

View from the heart: cardiac fibroblasts in development, scarring and regeneration

“…Fibrosis also causes exacerbated collagen deposition, which increases myocardial stiffness. Since fibroblasts are capable of coupling through gap junctions with each other and with cardiomyocytes, scar areas are considered electrically conductive (Kakkar and Lee, 2010;Kohl and Gourdie, 2014). Indeed, cardiac fibroblasts express a broad range of ionic channels and calcium-handling proteins and are capable of transducing electrical information received from the microenvironment (Camelliti et al, 2005).…”

Electrotonic coupling of excitable and nonexcitable cells in the heart revealed by optogenetics

“…Nonmyocytes, mainly interstitial and endothelial cells, represent a heterogeneous, dynamic group of nonexcitable cells that outnumber myocytes, although they occupy a smaller volume fraction (2). Whereas paracrine and structural roles of nonmyocytes are wellestablished in the mammalian heart, awareness of their potential role in electrical signal propagation has only started to emerge (3,4).…”

Congenital Heart Disease: In Search of Remedial Etiologies

“…We propose to exploit our findings using the single cell engraftment model to deliver relevant payloads to connective tissues of hearts with visible congenital malformations, e.g., valves, septa, hypoplastic ventricles, or non-compacted myocardium in which growth has been compromised. We include myocardial growth malformations because there is emerging evidence that fibroblasts establish heterotypic contacts in vivo with myocytes that can affect myocyte growth or electrophysiology [45]. For example, isolated CD45+ bone marrow cells could be genetically engineered to secrete growth factors like neuregulin which has been shown to reactivate cell cycling in mononucleated cardiomyocytes [46].…”