Cardiac length dependence of force and force redevelopment kinetics with altered cross-bridge cycling
Cardiac length dependence of force and force redevelopment kinetics with altered cross-bridge cycling
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DOI：
10.1529/biophysj.103.039131
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发表时间：
2004-09-01
影响因子：
3.4
通讯作者：
Martyn, DA
中科院分区：
文献类型：
--
作者：
Adhikari, BB;Regnier, M;Martyn, DA
我们研究了跨桥循环动力学对稳态力的长度依赖性和在肌节长度（SL）为2.0和2.3 μ m的剥皮大鼠心脏小梁的Ca 2+激活过程中的力重建率（k（tr））的影响。通过用2-脱氧-ATP（dATP）替换ATP或通过减少[ ATP]来改变跨桥动力学。在每个SL，dATP增加最大力（F-max）和力的Ca 2+敏感性（pCa（50）），并降低力-pCa关系的协同性（n（H）），而将[ATP]降低至0.5 mM（低ATP）增加pCa（50）和n（H），而不改变F-max。SL 2.0和2.3 mum之间的pCa（50）差异（Δ PCa（50））在ATP和dATP之间相当，但在低ATP下降低。最大k（tr）由dATP升高，由低ATP降低。Ca 2+敏感性的K（TR）增加与dATP和低ATP，并在所有条件下改变SL的影响。值得注意的是，在同等水平的次大力k（tr）是更快的短SL或增加晶格间距。这些数据表明，SL依赖的力取决于跨桥动力学和SL扩展时的力的增加发生而不增加之间的非力和力生成跨桥状态的过渡率，这表明SL或晶格间距可能调制预力跨桥过渡。
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 Ca2+-activation at sarcomere lengths (SL) of 2.0 and 2.3 mum 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 Ca2+-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 mum (DeltapCa(50)) was comparable between ATP and dATP, but reduced with low ATP. Maximal k(tr) was elevated by dATP and reduced by low ATP. Ca2+-sensivity 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.