© 1999 American Heart Association, Inc.
Editorial |
Plasticity in the Dynamics of Myocardial Contraction
Ca2+, Crossbridge Kinetics, or Molecular Cooperation
From the Department of Physiology, U.W. Cardiovascular Research Center, University of Wisconsin Medical School, Madison, Wis.
Correspondence to Richard L. Moss, PhD, Department of Physiology, U.W. Cardiovascular Research Center, University of Wisconsin Medical School, Madison, WI 53706. E-mail rlmoss@physiology.wisc.edu
Key Words: myocardium • contraction • kinetics • regulation • Ca2+
The myocardial twitch exhibits remarkable
plasticity in terms of peak developed force and the kinetics of force
development and relaxation. In the heart, such plasticity contributes
to beat-to-beat adjustments in stroke volume and to changes in cardiac
output as a consequence of altered sympathetic tone. There is ample
awareness of some of the mechanisms underlying the variability in the
cardiac twitch, including the Frank-Starling mechanism1
and neurohumoral modulation of cardiac
contractility.2 3 At the same time, the
molecular mechanisms by which the twitch is altered are not completely
understood, although most investigators would attribute changes in the
twitch to a combination of alterations in Ca2+
delivery to the myoplasm, Ca2+ sensitivity of
regulatory proteins, and kinetics of crossbridge interaction with
actin. These are interactive variables in the sense that changes in
Ca2+ delivery or Ca2+
sensitivity would be expected to change crossbridge interaction
kinetics. Cooperative interactions among contractile and regulatory
proteins comprise yet another variable that appears to regulate
crossbridge interaction in myocardium, ie, most
contemporary models include cooperativity as part of the
Ca2+ activation process.4 5 6
Cooperation does not appear as a single process, but it most likely
involves a combination of positive cooperativity in
Ca2+ binding to the thin filament as well as
effects of crossbridges to enhance Ca2+ binding,
to enhance further crossbridge binding, and to speed the rate of
crossbridge binding.6 Although cooperative mechanisms such
as these might contribute significantly to the cardiac twitch, we do
not yet know the degree to which these mechanisms contribute to the
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