Deletion of 1-43 amino acids in cardiac myosin essential light chain blunts length dependency of Ca2+ sensitivity and cross-bridge detachment kinetics

Michael JJ, Gollapudi SK, Ford SJ, Kazmierczak K, Szczesna-Cordary D, Chandra M. Deletion of 1-43 amino acids in cardiac myosin essential light chain blunts length dependency of Ca2(+) sensitivity and cross-bridge detachment kinetics. Am J Physiol Heart Circ Physiol 304: H253-H259, 2013. First published November 9, 2012; doi:10.1152/ajpheart.00572.2012.-The role of cardiac myosin essential light chain (ELC) in the sarcomere length (SL) dependency of myofilament contractility is unknown. Therefore, mechanical and dynamic contractile properties were measured at SL 1.9 and 2.2 mu m in cardiac muscle fibers from two groups of transgenic (Tg) mice: 1) Tg-wild-type (WT) mice that expressed WT human ventricular ELC and 2) Tg-Delta 43 mice that expressed a mutant ELC lacking 1-43 amino acids. In agreement with previous studies, Ca2(+)-activated maximal tension decreased significantly in Tg-Delta 43 fibers. pCa(50) (-log(10) [Ca2(+)](free) required for half maximal activation) values at SL of 1.9 mu m were 5.64 +/- 0.02 and 5.70 +/- 0.02 in Tg-WT and Tg-Delta 43 fibers, respectively. pCa(50) values at SL of 2.2 mu m were 5.70 +/- 0.01 and 5.71 +/- 0.01 in Tg-WT and Tg-Delta 43 fibers, respectively. The SL-mediated increase in the pCa(50) value was statistically significant only in Tg-WT fibers (P < 0.01), indicating that the SL dependency of myofilament Ca2(+) sensitivity was blunted in Tg-Delta 43 fibers. The SL dependency of cross-bridge (XB) detachment kinetics was also blunted in Tg-Delta 43 fibers because the decrease in XB detachment kinetics was significant (P < 0.001) only at SL 1.9 mu m. Thus the increased XB dwell time at the short SL augments Ca2(+) sensitivity at short SL and thus blunts SL-mediated increase in myofilament Ca2(+) sensitivity. Our data suggest that the NH2-terminal extension of cardiac ELC not only augments the amplitude of force generation, but it also may play a role in mediating the SL dependency of XB detachment kinetics and myofilament Ca2(+) sensitivity.