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-adrenergic-induced acceleration of cardiac
relaxation
1 Department of Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153; and 2 Department of Pharmacology and Cell Biophysics, College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267
Activation of
cAMP-dependent protein kinase A (PKA) in ventricular myocytes by
isoproterenol (Iso) causes phosphorylation of both phospholamban
(PLB) and troponin I (TnI) and accelerates relaxation by up to twofold.
Because PLB phosphorylation increases sarcoplasmic reticulum (SR) Ca
pumping and TnI phosphorylation increases the rate of Ca dissociation
from the myofilaments, both factors could contribute to the
acceleration of relaxation seen with PKA activation. To compare
quantitatively the role of TnI versus PLB phosphorylation, we measured
relaxation rates before and after maximal Iso treatment for twitches of
matched amplitudes in ventricular myocytes and muscle from wild-type
(WT) mice and from mice in which the PLB gene was knocked out (PLB-KO).
Because Iso increases contractions, even in the PLB-KO mouse,
extracellular [Ca] or sarcomere length was adjusted to
obtain matching twitch amplitudes (in the presence and absence of Iso).
In PLB-KO myocytes and muscles (which were allowed to shorten), Iso did
not alter the time constant (
) of relaxation (~29 ms). However,
with increasing isometric force development in the PLB-KO muscles, Iso
progressively but modestly accelerated relaxation (by 17%). These
results contrast with WT myocytes and muscles where Iso greatly reduced
of cell relaxation and intracellular Ca concentration decline (by
30-50%), independent of mechanical load. The Iso treatment used
produced comparable increases in phosphorylation of TnI and PLB in WT. We conclude that the effect of 
-adrenergic activation on relaxation is mediated entirely by PLB phosphorylation in the absence of external
load. However, TnI phosphorylation could contribute up to 14-18%
of this lusitropic effect in the WT mouse during maximal isometric contractions.
protein kinase A; relaxation; isoproterenol; calcium concentration
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