(Circulation. 2000;102:2249.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Chronic 
-Adrenergic Receptor Stimulation Modulates the Contractile Phenotype of Cardiac Myocytes In Vitro
From the Cardiovascular Section, Boston University Medical Center, Myocardial Biology Unit and Cardiac Muscle Research Laboratory, Boston University School of Medicine, Boston, Mass.
Correspondence to Dr Wilson S. Colucci, Cardiovascular Section, Boston University Medical Center, 88 E Newton St, Boston, MA 02118. E-mail wilson.colucci{at}bmc.org
Background—Heart failure is
characterized by contractile dysfunction of the myocardium
and elevated sympathetic activity. We tested the hypothesis that
chronic 
-adrenergic (-ADR) stimulation modifies the molecular and
contractile phenotype of cardiac myocytes.
Methods and Results—Adult rat ventricular
myocytes in culture were exposed to -ADR stimulation
(norepinephrine + propranolol) for 48 hours.
-ADR stimulation decreased the mRNAs for sarcoplasmic reticulum
Ca2+-ATPase and Ca2+ release channel by 56%
and 52%, respectively, and increased mRNA and protein for the
Na+-Ca2+ exchanger by 70% and 39%,
respectively. After washout of the -ADR agonist,
simultaneous measurement of
[Ca2+]i transients with fura 2 and
myocyte shortening by video edge-detection showed that
[Ca2+]i amplitude and myocyte shortening were
decreased in -ADR–treated myocytes, and the time to peak and time
from peak to 80% decline of both [Ca2+]i and
myocyte shortening were increased. The concentration-response curve for
myocyte shortening by the Na+ channel activator
veratridine was shifted leftward in -ADR–stimulated myocytes
(EC50, 21.6±4.6 versus 105.8±10.5 nmol/L,
P<0.001).
Conclusions—Chronic -ADR stimulation of cardiac myocytes
causes decreases in the expression of sarcoplasmic reticulum
Ca2+-ATPase and the Ca2+ release channel that
are associated with decreases in [Ca2+]i and
contractility. -ADR stimulation
simultaneously increases Na+-Ca2+
exchanger expression, thereby increasing sensitivity to intracellular
Na+.
Key Words: myocytes • calcium • sarcoplasmic reticulum • ion channels • receptors, adrenergic, alpha
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