Determinants of velocity of sarcomere shortening in mammalian myocardium.

Abstract

Maximal unloaded velocity of shortening of cardiac muscle (Vo) depends on the level of activation of the contractile filaments. We have tested the hypothesis that this dependence may be caused by viscous resistance of the muscle to length changes. Twitch force (Fo) and sarcomere shortening were studied in trabeculae dissected from the right ventricle of rat myocardium, superfused with modified Krebs-Henseleit solution at 25 degrees C. Sarcomere length (SL) was measured by laser diffraction techniques; force was measured by a silicon strain gauge; velocity of sarcomere shortening was measured using the "isovelocity release" technique. Vo and Fo at slack SL were a sigmoidal function of [Ca2+]o, but Vo was more sensitive to [Ca2+]o (Km: 0.44 +/- 0.04 mM) than isometric twitch force (Km: 0.68 +/- 0.03 mM). At [Ca2+]o = 1.5 mM, Vo was independent of SL above 1.9 microns, but depended on SL at lower [Ca2+]o and always depended on SL < 1.9 microns. A constant relation was observed between Vo and Fo, irrespective whether Fo was altered by variation of [Ca2+]o or SL above slack length. Visco-elastic properties of unstimulated muscles were studied at SL = 2.0 microns by small linear length changes at varied velocities up to 40 microns/s. The force response to stretch, after correction for the contribution of static parallel elasticity, consisted of an exponential increase of force (tau = 4 ms) and an exponential decline after the stretch. This response would be expected from an arrangement of a viscous element in series with an elastic element. Viscous force increased in proportion to stretch velocity by 0.2-0.5% of Fo/micron/s up to 15 microns/s, while the calculated stiffness of the elastic component was 25-45 N.mm-3, suggesting that the most likely structural candidate for this visco-elastic element is titin. Dynamic stiffness at 500 Hz was proportional to instantaneous force during shortening and was 12% of stiffness at maximal twitch force when shortening occurred at Vo. This suggests that the number of active force generators, even at maximal activation, is strongly reduced during shortening at Vo. The observed relation between Vo and Fo could be explained by a model in which shortening velocity of the cardiac sarcomere depends on the level of activation and hence on the number of cross bridges supporting the viscous load.