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1 Department of Physiology, University of Kentucky, Lexington, Kentucky, United States
* To whom correspondence should be addressed. E-mail: k.s.campbell{at}uky.edu.
Isolated cardiac muscles generate tension more quickly at higher levels of Ca2+ activation. We investigated the molecular mechanisms underlying this effect in permeabilized rat myocardial preparations by measuring the rate of tension recovery following brief shortening/re-stretch perturbations. Separate series of experiments used Ca2+-activating solutions with different pH values (pH 6.75, 7.00 and 7.25) and different phosphate (Pi) concentrations (0, 2.5 and 5.0 mM added Pi) to modulate the recovery kinetics. Subsequent analysis showed that the rate of tension recovery correlated (p<0.001) with the relative residual tension, that is, the minimum tension measured immediately after re-stretch normalized to the steady-state isometric tension for the experimental condition. This new finding suggests that the rate at which cardiac muscles develop force increases with the proportion of cross-bridges bound to the thin filament and is strong evidence of cooperative contractile activation.
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