Force suppression and the crossbridge cycle in swine carotid artery.
Force suppression and the crossbridge cycle in swine carotid artery.
复制标题
猪颈动脉的力抑制和横桥循环。
DOI：
10.1152/ajpcell.00091.2007
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Rembold,ChristopherM
中科院分区：
文献类型：
--
作者：
Rembold,ChristopherM
环核苷酸可以松弛动脉平滑肌，而不会减少交叉桥的磷酸化，这一过程被称为力抑制。有两种潜在的力抑制机制：1)与细丝结合的磷酸化交叉桥可以被抑制，或者2)细丝与锚定结构的附着可能被破坏。这些机制是通过比较组胺刺激的猪动脉平滑肌在有和没有Forsklin诱导的力量抑制以及有和没有Latrunculin-A诱导的肌动蛋白细丝断裂的情况下进行的。与无力抑制的组织相比，在匹配的力抑制下，与低负荷下的组织相比，力抑制与更高的交叉桥磷酸化和更短的速度相关。高载荷下的缩短速度、噪声温度、磁滞和刚度在加力和不加力的情况下没有差别。这些数据表明，在力抑制过程中，交叉桥的磷酸化调节交叉桥周期。与没有破坏肌动蛋白的组织相比，使用Latrunculin-A的肌动蛋白破坏与更高的交叉桥磷酸化有关。缩短速度、噪声温度、滞后和僵硬在肌动蛋白中断和不中断的情况下没有差别。这些数据表明，肌动蛋白的破坏干扰了交叉桥磷酸化对交叉桥循环的调节。僵硬与应力呈线性关系，这表明每个附着的交叉桥的作用力不会随力抑制或肌动蛋白破坏而改变。这些数据表明，在力抑制和肌动蛋白破坏过程中观察到的力学特征有所不同，这意味着力抑制从机械上讲并不涉及肌动蛋白破坏。这些数据与力抑制涉及抑制磷酸化的交叉桥与细丝结合的模型最一致。
Cyclic nucleotides can relax arterial smooth muscle without reductions in crossbridge phosphorylation, a process termed force suppression. There are two potential mechanisms for force suppression:1) phosphorylated crossbridges binding to thin filaments could be inhibited or2) the attachment of thin filaments to anchoring structures could be disrupted. These mechanisms were evaluated by comparing histamine-stimulated swine arterial smooth muscle with and without forskolin-induced force suppression and with and without latrunculin-A-induced actin filament disruption. At matched force, force suppression was associated with higher crossbridge phosphorylation and shortening velocity at low loads when compared with tissues without force suppression. Shortening velocity at high loads, noise temperature, hysteresivity, and stiffness did not differ with and without force suppression. These data suggest that crossbridge phosphorylation regulates the crossbridge cycle during force suppression. Actin disruption with latrunculin-A was associated with higher crossbridge phosphorylation when compared with tissues without actin disruption. Shortening velocity, noise temperature, hysteresivity, and stiffness did not differ with and without actin disruption. These data suggest that actin disruption interferes with regulation of crossbridge cycling by crossbridge phosphorylation. Stiffness was linearly dependent on stress, suggesting that the force per attached crossbridge was not altered with force suppression or actin disruption. These data suggest a difference in the mechanical characteristics observed during force suppression and actin disruption, implying that force suppression does not mechanistically involve actin disruption. These data are most consistent with a model where force suppression involves the inhibition of phosphorylated crossbridge binding to thin filaments.