Titin-Based Modulation of Calcium Sensitivity of Active Tension in Mouse Skinned Cardiac Myocytes

Abstract—We studied the effect of titin-based passive force on the length dependence of activation of cardiac myocytes to explore whether titin may play a role in the generation of systolic force. Force-pCa relations were measured at sarcomere lengths (SLs) of 2.0 and 2.3 μm. Passive tension at 2.3 μm SL was varied from ≈1 to ≈10 mN/mm2 by adjusting the characteristics of the stretch imposed on the passive cell before activation. Relative to 2.0 μm SL, the force-pCa curve at 2.3 μm SL and low passive tension showed a leftward shift (ΔpCa50 [change in pCa at half-maximal activation]) of 0.09±0.02 pCa units while at 2.3 μm SL and high passive tension the shift was increased to 0.25±0.03 pCa units. Passive tension also increased ΔpCa50 at reduced interfilament lattice spacing achieved with dextran. We tested whether titin-based passive tension influences the interfilament lattice spacing by measuring the width of the myocyte and by using small-angle x-ray diffraction of mouse left ventricular wall muscle. Ce...