Relaxation, [Ca2+]i, and the latch-bridge hypothesis in swine arterial smooth muscle.
Relaxation, [Ca2+]i, and the latch-bridge hypothesis in swine arterial smooth muscle.
复制标题
猪动脉平滑肌的松弛、[Ca2]i 和闩桥假说。
DOI：
10.1152/ajpcell.1991.261.1.c41
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Rembold,CM
中科院分区：
文献类型：
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作者：
Rembold,CM
在血管平滑肌松弛过程中，肌球蛋白轻链磷酸化值比应激值更快地降至静息值。由于磷酸化程度较低，锁桥假说预测松弛过程中的应力应主要由锁桥承担。我通过改变组织长度并在猪颈动脉内侧组织松弛期间用水母发光蛋白测量肌质 Ca2+ 浓度 ([Ca2+]) 来评估锁桥的机械性能。压力的产生是用 Hai 和 Murphy 的锁桥模型预测的，其中测量的水母蛋白 [Ca2+] 信号是压力的唯一决定因素。基于水母发光蛋白的锁桥模型预测了组胺刺激消除后引起的松弛。然而，当组织在持续存在组胺的情况下通过去除细胞外Ca2+或Ca(2+)通道阻滞剂而松弛时，基于水母发光蛋白的模型适度地低估了由此产生的松弛。这种低估很可能是由于磷酸化的 [Ca2+] 敏感性小幅增加造成的，因为磷酸化的 [Ca2+] 敏感性改变的模型可以更准确地预测由此产生的松弛。当组织短暂拉伸或缩短然后恢复到原始长度时，猪颈动脉的松弛时间过程没有显着改变。由于拉伸会分离跨桥，因此我修改了基于水母发光蛋白的锁桥模型以考虑拉伸引起的跨桥分离。由于[Ca2+]值在拉伸前后均略高于静息值，因此该模型预测磷酸化的跨桥可以重新连接、去磷酸化并形成新的锁桥。该模型预测除了拉伸后的最初几秒钟外都会放松。这些结果表明，闩桥重新连接对于解释放松期间拉伸的大部分反应不是必要的。松弛的限速步骤似乎是去除 [Ca2+]，而不是闩桥分离。
During vascular smooth muscle relaxation, myosin light-chain phosphorylation values decrease to resting values more rapidly than do stress values. Because phosphorylation is proportionally low, the latch-bridge hypothesis predicts that stress during relaxation should be predominantly carried by latch bridges. I evaluated the mechanical properties of latch bridges by changing tissue length and measuring myoplasmic Ca2+ concentration ([Ca2+]) with aequorin during relaxation of swine carotid medial tissues. Stress production was predicted with the latch-bridge model of Hai and Murphy, in which the measured aequorin [Ca2+] signal is the only determinant of stress. The aequorin-based latch-bridge model predicted relaxation induced by removal of the histamine stimulation. However, when tissues were relaxed by removal of extracellular Ca2+ or Ca(2+)-channel blockers in the continued presence of histamine, the aequorin-based model modestly underestimated the resulting relaxation. This underestimation was most likely caused by a small increase in the [Ca2+] sensitivity of phosphorylation since a model with an altered [Ca2+] sensitivity of phosphorylation more accurately predicted the resulting relaxation. The time course of relaxation in swine carotid artery was not substantially altered when the tissue was either briefly stretched or shortened and then returned to the original length. Because stretch should detach cross bridges, I modified the aequorin-based latch-bridge model to account for stretch-induced cross-bridge detachment. Because [Ca2+] values were slightly above resting values both before and after the stretch, the model predicted that phosphorylated cross bridges could reattach, be dephosphorylated, and form new latch bridges. The model predicted relaxation except during the first few seconds after stretch. These results suggest that latch-bridge reattachment is not necessary to explain the majority of the response to stretch during relaxation. The rate-limiting step for relaxation appears to be removal of [Ca2+] and not latch-bridge detachment.