Titin-based modulation of calcium sensitivity of active tension in mouse skinned cardiac myocytes

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 mum. Passive tension at 2.3 mum SL w as varied from approximate to1 to approximate to 10 mN/mm(2) by adjusting t he characteristics of the stretch imposed on the passive cell before activa tion. Relative to 2.0 mum Si,, the force-pCa curve at 2.3 mum SL and low pa ssive tension showed a leftward shift (Delta pCa(50) [change in pCa at half -maximal activation]) of 0.09 +/-0.02 pCa units while at 2.3 mum SL and hig h passive tension the shift was increased to 0.25 +/-0.03 pCa units. Passiv e tension also increased Delta pCa(50) at reduced interfilament lattice spa cing achieved with dextran. We tested whether titin-based passive tension i nfluences the interfilament lattice spacing by measuring the width of the m yocyte and by using small-angle x-ray diffraction of mouse left ventricular wall muscle. Cell width and interfilament lattice spacing varied inversely with passive tension, in the presence and absence of dextran. The passive tension effect on length-dependent activation may therefore result from a r adial titin-based force that modulates the interfilament lattice spacing.