Afm. Moorman et al., Presence of functional sarcoplasmic reticulum in the developing heart and its confinement to chamber myocardium, DEVELOP BIO, 223(2), 2000, pp. 279-290
During development fast-contracting atrial and ventricular chambers develop
from a peristaltic-contracting heart tube. This study addresses the questi
on of whether chamber formation is paralleled by a matching expression of t
he sarcoplasmic reticulum (SR) Ca2+ pump. We studied indo-1 Ca2+ transients
elicited by held stimulation of linear heart tube stages and of explants f
rom atria and outflow tracts of the prototypical preseptational E13 rat hea
rt. Ca2+ transients of H/H 11+ chicken hearts, which constitute the prototy
pic linear heart tube stage, were sensitive to verapamil only, indicating a
minor contribution of Ca2+-triggered SR Ca2+ release. Outflow tract transi
ents displayed sensitivity to the inhibitors similar to that of the linear
heart tube stages. Atrial Ca2+ transients disappeared upon addition of ryan
odine, tetracaine, or verapamil, indicating the presence of Ca2+-triggered
SR Ca2+ release. Quantitative radioactive in situ hybridization on sections
of E13 rat hearts showed similar to 10-fold higher SERCA2a mRNA levels in
the atria compared to nonmyocardial tissue and similar to 5-fold higher exp
ression in compact ventricular myocardium. The myocardium of atrioventricul
ar canal, outflow tract, inner curvature, and ventricular trabecules displa
yed weak expression. Immunohistochemistry on sections of rat and human embr
yos showed a similar pattern. The significance of these findings is threefo
ld. (i) A functional SR is present long before birth. (ii) SR development i
s concomitant with cardiac chamber development, explaining regional differe
nces in cardiac function. (iii) The pattern of SERCA2a expression underscor
es a manner of chamber development by differentiation at the outer curvatur
e, rather than by segmentation of the linear heart tube. (C) 2000 Academic
Press.