Two-state model of acto-myosin attachment-detachment predicts C-process of sinusoidal analysis
Two-state model of acto-myosin attachment-detachment predicts C-process of sinusoidal analysis
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DOI：
10.1529/biophysj.106.101626
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发表时间：
2007-08-01
影响因子：
3.4
通讯作者：
Maughan, David W.
中科院分区：
文献类型：
--
作者：
Palmer, Bradley M.;Suzuki, Takeki;Maughan, David W.
激活的横纹肌对长度扰动的力响应包括所谓的C过程，其被认为是长度步长（阶段1和阶段2）后快速单指数力衰减的频域表示。然而，这种现象的潜在分子机制仍然是各种假说的主题。在这项研究中，我们推导出了解析表达式，并创建了一个相应的计算机模型来描述独立的acto-myosin跨桥的后果，其特征仅在于：1），附着（t（att））和分离（t（det））的间歇期，其值由独立的概率密度函数随机支配; 2），有限的胡克刚度（k（stiff））仅在附着期间有效。通过频域中的解析表达式预测了组成半肌节的20，000（N）个交叉桥（F-hs（t））对正弦长度扰动（L-hs（t））的计算机模拟力响应，（（F）（hs）（Ω）/（L）（hs）（Ω））=（（t）（att）/（t）（cycle））N（k）（stiff）（i ω/（t）over bar（-1）（att）+ i ω）），其中（t）over bar（att）=（t）over bar（att）的平均值，（t）over bar（cycle）= t（att）+ t（det）的平均值，（k）over bar（stiff）=平均刚度，以及ω = 2 π x扰动频率。此外，通过时域中的解析表达式F-hs（t）=（（t）over bar（att）/（t）over bar（cycle））N（k）over bar L-stiff（hs）e（-t/tatt）来预测由长度步长（L-hs）引起的模拟力响应。这些解析推导的表达式的形式是一致的表达历史上用来描述这些特定的特征的力响应，并建议的动作肌球蛋白跨桥和其相关的刚度的循环是负责的C-过程和阶段1和2。速率常数2 π c，即，历史上定义的C过程的频率参数在这里显示为等于（t）除以bar（-1）（att）。发现在不同温度下检查并主要含有α-或β-肌球蛋白重链同种型的活化心肌的实验结果与上述解释一致。
The force response of activated striated muscle to length perturbations includes the so-called C-process, which has been considered the frequency domain representation of the fast single-exponential force decay after a length step (phases 1 and 2). The underlying molecular mechanisms of this phenomenon, however, are still the subject of various hypotheses. In this study, we derived analytical expressions and created a corresponding computer model to describe the consequences of independent acto-myosin cross-bridges characterized solely by 1), intermittent periods of attachment (t(att)) and detachment (t(det)), whose values are stochastically governed by independent probability density functions; and 2), a finite Hookian stiffness (k(stiff)) effective only during periods of attachment. The computer-simulated force response of 20,000 (N) cross-bridges making up a half-sarcomere (F-hs(t)) to sinusoidal length perturbations (L-hs(t)) was predicted by the analytical expression in the frequency domain, ((F) over tilde (hs) (omega)/ (L) over tilde (hs) (omega)) = ((t) over bar (att)/(t) over bar (cycle)) N (k) over bar (stiff)(i omega / (t) over bar (-1)(att) + i omega)), where (t) over bar (att) = mean value of (t) over bar (att), (t) over bar (cycle) = mean value of t(att) + t(det), (k) over bar (stiff) = mean stiffness, and omega = 2 pi x frequency of perturbation. The simulated force response due to a length step (L-hs) was furthermore predicted by the analytical expression in the time domain, F-hs(t) = ((t) over bar (att)/(t) over bar (cycle))N (k) over bar L-stiff(hs) e(-t/tatt). The forms of these analytically derived expressions are consistent with expressions historically used to describe these specific characteristics of a force response and suggest that the cycling of acto-myosin cross-bridges and their associated stiffnesses are responsible for the C-process and for phases 1 and 2. The rate constant 2 pi c, i.e., the frequency parameter of the historically defined C-process, is shown here to be equal to (t) over bar (-1)(att). Experimental results from activated cardiac muscle examined at different temperatures and containing predominately alpha- or beta-myosin heavy chain isoforms were found to be consistent with the above interpretation.