Length Dependence of Cardiac Myofilament Ca2+ Sensitivity in the Presence of Substitute Nucleoside Triphosphates

Abstract Although ATP is the immediate source of energy for muscle contraction other nucleoside triphosphates (NTP) can substitute for ATP as substrates for myosin and as sources of energy for contraction of skinned muscle fibers. However, experiments with skinned skeletal muscle fibers in the presence of substitute NTP indicate significant differences with respect to cross-bridge kinetics, force generation, and Ca 2+ regulation. In this study the length dependence of Ca 2+ sensitivity of skinned bovine cardiac muscle was analyzed in the presence of MgATP, MgCTP, MgUTP, and MgITP. Ca 2+ regulation in the presence of MgCTP and MgUTP was essentially the same as in the presence of MgATP, although the maximum force generated (at sarcomere length 2.4 μ m) was about 25% less. However, the length dependence of Ca 2+ sensitivity was eliminated in the presence of MgUTP. With MgITP the maximum force generated (at sarcomere length 2.4 μ m) was about the same as in the presence of MgATP, but there was an impairment of relaxation such that at pCa 8 the force developed was about 50–60% of that developed at pCa 5. Moreover, the Ca 2+ -dependent component showed no length-dependent sensitivity. Thus length modulation of Ca 2+ sensitivity is a function of the myosin substrate. Taken in conjunction with other data, the results are consistent with the hypothesis that length-dependence of Ca 2+ sensitivity is modulated at a step upstream from the force-generating reaction.