© 1995 American Heart Association, Inc.
Articles |
Spatial Distribution of Connexin43, the Major Cardiac Gap Junction Protein, Visualizes the Cellular Network for Impulse Propagation From Sinoatrial Node to Atrium
From the Department of Physiology (I. ten V., B. de J., E.E.V.), University of Amsterdam (Netherlands); Laboratoire de Génétique et Physiologie du Développement (D.G.), Faculté des Sciences de Luminy, Université d'Aix-Marseille II (France); and the Department of Medical Physiology and Sports Medicine (M.J.A. van K., L.A., H.J.J.), University of Utrecht (Netherlands).
Abstract Myocytes are electrically coupled by gap junctions,
which are composed of low-resistance intercellular channels. The major
cardiac gap junction protein is connexin43 (Cx43). The distribution of
Cx43 has been studied by immunofluorescence to visualize the electrical
coupling between atrial tissue and sinoatrial node. From modeling
studies, this coupling was inferred to be gradual in order to shield
the sinoatrial node from the atrial hyperpolarizing influence. The
actual Cx43 labeling pattern did not show the expected gradient but
instead a rather black and white staining in a striking pattern of
strands of cells. We used an immunohistochemical marker
(anti–
-smooth muscle actin [SMA]) that specifically
cross-reacts with guinea pig sinoatrial node cells together with Cx43
antibody to stain previously electrophysiologically mapped sinoatrial
nodes. We found that in the guinea pig sinoatrial node the impulse
originates in an SMA-positive, virtually Cx43-negative, region
(primary pacemaker region). The impulse then travels obliquely upward
to the crista terminalis through a region where layers of
SMA-positive cells alternate with layers of Cx43-positive
SMA-negative cells. The layers of Cx43-positive cells appear to become
broader and thicker in the direction of the crista terminalis, whereas
the layers of SMA-positive cells become thinner and narrower.
Lateral contacts between Cx43- and SMA-positive cells were very
sparse and only detected where the Cx43-positive strands ended (the
region where SMA-positive cells fill the whole space between
endocardium and epicardium, ie, the putative primary pacemaker region).
From these results, we conclude that the primary pacemaker is shielded
from the hyperpolarizing influence of the atrium by a gradient in
coupling brought about by tissue geometric factors rather than by a
gradient of gap junction density.
Key Words: gap junctions • connexin43 • sinoatrial node • immunofluorescence • impulse conduction
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