Deletion of 1-43 Amino Acids in Cardiac Myosin Essential

31 The role of cardiac myosin essential light chain (ELC) in the sarcomere length (SL)-dependency 32 of myofilament contractility is unknown. Therefore, mechanical and dynamic contractile 33 properties were measured at SL 1.9 μm and 2.2 μm in cardiac muscle fibers from two groups of 34 transgenic (Tg) mice: 1) Tg-wild type (WT) mice that expressed wild type human ventricular 35 ELC; and 2) Tg-Δ43 mice that expressed a mutant ELC lacking 1-43 amino acids. In agreement 36 with previous studies, Ca-activated maximal tension decreased significantly in Tg-Δ43 fibers. 37 pCa50 (-log10 [Ca]free required for half maximal activation) values at SL of 1.9 μm were: 5.64 ± 38 0.02 and 5.70 ± 0.02 in Tg-WT and Tg-Δ43 fibers, respectively. pCa50 values at SL of 2.2 μm 39 were: 5.70 ± 0.01 and 5.71 ± 0.01 in Tg-WT and Tg-Δ43 fibers, respectively. The SL-mediated 40 increase in the pCa50 value was statistically significant only in Tg-WT fibers (P < 0.01), 41 indicating that the SL-dependency of myofilament Ca sensitivity was blunted in Tg-Δ43 fibers. 42 The SL-dependency of XB detachment kinetics was also blunted in Tg-Δ43 fibers because the 43 decrease in XB detachment kinetics was significant (P<0.001) only at SL 1.9 μm. Thus, the 44 increased XB dwell time at the short SL augments Ca sensitivity at short SL and thus blunts 45 SL-mediated increase in myofilament Ca sensitivity. Our data suggests that the N-terminal 46 extension of cardiac ELC not only augments the amplitude of force generation, but it also may 47 play a role in mediating the SL-dependency of XB detachment kinetics and myofilament Ca 48 sensitivity. 49