Deletion of 1-43 amino acids in cardiac myosin essential light chain blunts length dependency of Ca(2+) sensitivity and cross-bridge detachment kinetics.
Deletion of 1-43 amino acids in cardiac myosin essential light chain blunts length dependency of Ca(2+) sensitivity and cross-bridge detachment kinetics.
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心肌肌球蛋白必需轻链中 1-43 个氨基酸的缺失减弱了 Ca(2) 敏感性和跨桥脱离动力学的长度依赖性。
DOI：
10.1152/ajpheart.00572.2012
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发表时间：
2013
期刊：
影响因子：
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通讯作者：
Chandra,Murali
中科院分区：
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作者：
Michael,JohnJeshurun;Gollapudi,SampathK;Ford,StevenJ;Kazmierczak,Katarzyna;Szczesna-Cordary,Danuta;Chandra,Murali
心肌肌球蛋白必需轻链（ELC）在肌丝收缩的肌节长度（SL）依赖性中的作用尚不清楚。因此，在SL 1.9和2.2 μm处测量了两组转基因（Tg）小鼠心肌纤维的机械和动态收缩特性：1）表达WT人心室ELC的Tg-野生型（WT）小鼠和2）表达缺失1-43个氨基酸的突变ELC的Tg-Δ43小鼠。与先前的研究一致，Tg-Δ43纤维中的Ca 2+激活的最大张力显著降低。Tg-WT和Tg-Δ43纤维在SL为1.9 μm时的pCa 50（半数最大激活所需的− log 10 [Ca 2 +] free）值分别为5.64 ± 0.02和5.70 ± 0.02。在2.2 μm的SL下，Tg-WT和Tg-Δ43纤维的pCa 50值分别为5.70 ± 0.01和5.71 ± 0.01。SL介导的pCa 50值的增加仅在Tg-WT纤维中具有统计学意义（P< 0.01），表明在Tg-Δ43纤维中SL对肌丝Ca 2+敏感性的依赖性减弱。在Tg-Δ43纤维中，横桥（XB）脱离动力学的SL依赖性也被钝化，因为XB脱离动力学的降低仅在SL 1.9 μm处显著（P< 0.001）。因此，在短SL下增加的XB停留时间增加了在短SL下的Ca 2+敏感性，从而减弱了SL介导的肌丝Ca 2+敏感性的增加。我们的数据表明，心脏ELC的NH 2-末端延伸不仅增加了力产生的幅度，但它也可能在介导XB脱离动力学和肌丝Ca 2+敏感性的SL依赖性中发挥作用。
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 μm in cardiac muscle fibers from two groups of transgenic (Tg) mice:1) Tg-wild-type (WT) mice that expressed WT human ventricular ELC and2) Tg-Δ43 mice that expressed a mutant ELC lacking 1–43 amino acids. In agreement with previous studies, Ca2+-activated maximal tension decreased significantly in Tg-Δ43 fibers. pCa50(−log10[Ca2+]freerequired for half maximal activation) values at SL of 1.9 μm were 5.64 ± 0.02 and 5.70 ± 0.02 in Tg-WT and Tg-Δ43 fibers, respectively. pCa50values at SL of 2.2 μm were 5.70 ± 0.01 and 5.71 ± 0.01 in Tg-WT and Tg-Δ43 fibers, respectively. The SL-mediated increase in the pCa50value was statistically significant only in Tg-WT fibers (P< 0.01), indicating that the SL dependency of myofilament Ca2+sensitivity was blunted in Tg-Δ43 fibers. The SL dependency of cross-bridge (XB) detachment kinetics was also blunted in Tg-Δ43 fibers because the decrease in XB detachment kinetics was significant (P< 0.001) only at SL 1.9 μm. 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.