Adhikari Bishow B, Regnier Michael, Rivera Anthony J, Kreutziger Kareen L, Martyn Donald A
Department of Bioengineering, University of Washington, Seattle Washington 98195, USA.
Biophys J. 2004 Sep;87(3):1784-94. doi: 10.1529/biophysj.103.039131.
We examined the influence of cross-bridge cycling kinetics on the length dependence of steady-state force and the rate of force redevelopment (k(tr)) during Ca(2+)-activation at sarcomere lengths (SL) of 2.0 and 2.3 microm in skinned rat cardiac trabeculae. Cross-bridge kinetics were altered by either replacing ATP with 2-deoxy-ATP (dATP) or by reducing [ATP]. At each SL dATP increased maximal force (F(max)) and Ca(2+)-sensitivity of force (pCa(50)) and reduced the cooperativity (n(H)) of force-pCa relations, whereas reducing [ATP] to 0.5 mM (low ATP) increased pCa(50) and n(H) without changing F(max). The difference in pCa(50) between SL 2.0 and 2.3 microm (Delta pCa(50)) was comparable between ATP and dATP, but reduced with low ATP. Maximal k(tr) was elevated by dATP and reduced by low ATP. Ca(2+)-sensitivity of k(tr) increased with both dATP and low ATP and was unaffected by altered SL under all conditions. Significantly, at equivalent levels of submaximal force k(tr) was faster at short SL or increased lattice spacing. These data demonstrate that the SL dependence of force depends on cross-bridge kinetics and that the increase of force upon SL extension occurs without increasing the rate of transitions between nonforce and force-generating cross-bridge states, suggesting SL or lattice spacing may modulate preforce cross-bridge transitions.
我们研究了在大鼠去皮肤心脏小梁肌节长度（SL）为2.0和2.3微米时，跨桥循环动力学对稳态力的长度依赖性以及Ca(2+)激活过程中力重建速率（k(tr)）的影响。通过用2-脱氧-ATP（dATP）替代ATP或降低[ATP]来改变跨桥动力学。在每个SL下，dATP增加了最大力（F(max)）和力的Ca(2+)敏感性（pCa(50)），并降低了力-pCa关系的协同性（n(H)），而将[ATP]降低到0.5 mM（低ATP）则增加了pCa(50)和n(H)，同时不改变F(max)。SL 2.0和2.3微米之间的pCa(50)差异（ΔpCa(50)）在ATP和dATP之间相当，但在低ATP时降低。最大k(tr)被dATP升高，被低ATP降低。k(tr)的Ca(2+)敏感性在dATP和低ATP时均增加，并且在所有条件下均不受改变的SL的影响。值得注意的是，在次最大力水平相当的情况下，k(tr)在短SL或增加晶格间距时更快。这些数据表明，力的SL依赖性取决于跨桥动力学，并且SL延长时力的增加是在不增加非力和产生力的跨桥状态之间转换速率的情况下发生的，这表明SL或晶格间距可能调节预力跨桥转换。
