Dynamic coupling of regulated binding sites and cycling myosin heads in striated muscle

被引:34
作者
Campbell, Kenneth S. [1 ,2 ]
机构
[1] Univ Kentucky, Dept Physiol, Lexington, KY 40536 USA
[2] Univ Kentucky, Ctr Muscle Biol, Lexington, KY 40536 USA
基金
美国国家卫生研究院;
关键词
SKELETAL-MUSCLE; COOPERATIVE REGULATION; MECHANICAL-PROPERTIES; RABBIT PSOAS; ACTIN INTERACTIONS; KINESIN MOLECULES; TENSION RECOVERY; HALF-SARCOMERE; FORCE; FIBERS;
D O I
10.1085/jgp.201311078
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
In an activated muscle, binding sites on the thin filament and myosin heads switch frequently between different states. Because the status of the binding sites influences the status of the heads, and vice versa, the binding sites and myosin heads are dynamically coupled. The functional consequences of this coupling were investigated using MyoSim, a new computer model of muscle. MyoSim extends existing models based on Huxley-type distribution techniques by incorporating Ca2+ activation and cooperative effects. It can also simulate arbitrary cross-bridge schemes set by the researcher. Initial calculations investigated the effects of altering the relative speeds of binding-site and cross-bridge kinetics, and of manipulating cooperative processes. Subsequent tests fitted simulated force records to experimental data recorded using permeabilized myocardial preparations. These calculations suggest that the rate of force development at maximum activation is limited by myosin cycling kinetics, whereas the rate at lower levels of activation is limited by how quickly binding sites become available. Additional tests investigated the behavior of transiently activated cells by driving simulations with experimentally recorded Ca2+ signals. The unloaded shortening profile of a twitching myocyte could be reproduced using a model with two myosin states, cooperative activation, and strain-dependent kinetics. Collectively, these results demonstrate that dynamic coupling of binding sites and myosin heads is important for contractile function.
引用
收藏
页码:387 / 399
页数:13
相关论文
共 51 条
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