A distribution-moment model of deactivation in cardiac muscle

The Distribution-Moment (DEVI) model has simulated experimental data on ske letal muscle, but it has not been used previously to study the mechanics of active contraction in cardiac muscle. In contrast to previous models of st riated muscle contraction, all parameters have physical meaning and assumpt ions concerning biophysical events within the cell are consistent with avai lable data. In order to stimulate cardiac muscle deactivation using the DM model it was necessary to make the cross-bridge detachment rates large for large displacements from the neutral equilibrium position of a cross-bridge . To examine the effect of cooperativity on cardiac muscle contraction, we used the DM model's tight coupling scheme with binding of one or two calciu m sites regulating contraction. As observed experimentally, our model predi cted a reduction of isometric tension development following rapid shortenin g-lengthening transients when contraction is regulated by either one or two calcium binding sites. The predicted deactivating effect increased if the transient was applied late in the twitch when contraction is regulated by t wo calcium binding sites, but not when it is regulated by one site. This is the first study in which deactivation has been simulated without making an y provisions for length-dependent calcium-trononin dissociation. (C) 1998 E lsevier Science Ltd. All rights reserved.