Circulation Research. 2004;94:828-835
Published online before print February 19, 2004, doi: 10.1161/01.RES.0000122382.19400.14
Published online before print February 19, 2004, doi: 10.1161/01.RES.0000122382.19400.14
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© 2004 American Heart Association, Inc.
Integrative Physiology |
Fibroblast Network in Rabbit Sinoatrial Node
Structural and Functional Identification of Homogeneous and Heterogeneous Cell Coupling
From the University Laboratory of Physiology (P.C., P.K.), Oxford, UK; Departments of Anatomy with Radiology (C.R.G.) and of Physiology (I.L.), University of Auckland, Auckland, New Zealand.
Correspondence to Peter Kohl, University Laboratory of Physiology, Oxford, OX1 3PT, UK. E-mail peter.kohl{at}physiol.ox.ac.uk
Cardiomyocytes form a conducting network that is assumed to be electrically isolated from nonmyocytes in vivo. In cell culture, however, cardiac fibroblasts can contribute to the spread of excitation via functional gap junctions with cardiomyocytes. To assess the ability of fibroblasts to form gap junctions in vivo, we combine in situ detection of connexins in rabbit sinoatrial node (a tissue that is particularly rich in fibroblasts) with identification of myocytes and fibroblasts using immunohistochemical labeling and confocal microscopy. We distinguish two spatially distinct fibroblast populations expressing different connexins: fibroblasts surrounded by other fibroblasts preferentially express connexin40, whereas fibroblasts that are intermingled with myocytes largely express connexin45. Functionality of homogeneous and heterogeneous cell coupling was investigated by dye transfer in sinoatrial node tissue explants. These studies reveal spread of Lucifer yellow, predominantly along extended threads of interconnected fibroblasts (probably via connexin40), and occasionally between neighboring fibroblasts and myocytes (probably via connexin45). Our findings show that cardiac fibroblasts form a coupled network of cells, which may be functionally linked to myocytes in rabbit SAN.
Key Words: heart • connective tissue • pacemaker • gap junction • in vivo
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