Coordinate regulation of sarcoplasmic reticulum ca2+-atpase and
phospholamban expression in the developing murine heart.
Harrer, Judy M., Kobra Haghighi, Hae Won Kim, Donald G. Ferguson,
Evangelia G. Kranias.
Departments of Pharmacology and Cell Biophysics, Physiology and
Biophysics, University of Cincinnati, College of Medicine,
Cincinnati, Ohio, Department of Pharmacology, College of Medicine, Ul
San University, Seoul, Korea
APStracts 3:0268H, 1996.
Phospholamban, the regulator of the Ca2+-ATPase activity in cardiac
sarcoplasmic reticulum, is an important determinant of basal
myocardial performance. To determine whether phospholamban expression
is developmentally regulated in the mouse and whether such regulation
reflects alterations in Ca2+-pump activity, hearts from different
stages of development were processed for molecular biological and
biochemical studies. Both phospholamban and Ca2+-ATPase mRNAs were
approximately 40% of adult (100%) levels at birth and gradually
increased to approach adult levels by day 15 of development. These
changes in transcript levels were indicative of changes at the
protein level for both phospholamban and Ca2+-ATPase. Analysis of the
initial rates of Ca2+-uptake demonstrated that over the course of
development: 1) the up-regulation of the Ca2+-ATPase correlated with
increases in the maximal rates of Ca2+-uptake; and 2) the constant
apparent stoichiometric ratio of phospholamban to the Ca2+-ATPase
correlated with maintenance of a constant affinity of this enzyme for
Ca2+ (0.25 _symbol 177 \f "Symbol" \s 12__ 0.03 mM Ca2+).
Furthermore, targeted ablation of phospholamban in the mouse,
resulted in a much higher affinity of Ca2+-uptake for Ca2+ (0.10
_symbol 177 \f "Symbol" \s 12__ 0.02 mM Ca2+) than that
observed in wild-type hearts, and this increased affinity was also
maintained across different stages of postnatal development. These
findings suggest that phospholamban is a major regulator of the
affinity of the Ca2+-ATPase for Ca2+ and coordinate regulation of the
expression levels of these two sarcoplasmic reticulum proteins may be
necessary for maintaining Ca2+ homeostasis in the developing
mammalian heart.
Received 24 April 1996; accepted in final form 5 June 1996.
APS Manuscript Number H361-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96