Rembold C M
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.
Am J Physiol. 1991 Jul;261(1 Pt 1):C41-50. doi: 10.1152/ajpcell.1991.261.1.C41.
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.
在血管平滑肌舒张过程中，肌球蛋白轻链磷酸化值比应力值更快地降至静息值。由于磷酸化比例较低，闩锁桥假说预测舒张过程中的应力应主要由闩锁桥承担。我通过改变组织长度并在猪颈动脉中层组织舒张期间用水母发光蛋白测量肌浆Ca2+浓度（[Ca2+]）来评估闩锁桥的力学特性。应力产生是根据海和墨菲的闩锁桥模型预测的，其中测量到的水母发光蛋白[Ca2+]信号是应力的唯一决定因素。基于水母发光蛋白的闩锁桥模型预测了组胺刺激去除后引起的舒张。然而，当在组胺持续存在的情况下通过去除细胞外Ca2+或Ca(2+)通道阻滞剂使组织舒张时，基于水母发光蛋白的模型适度低估了由此产生的舒张。这种低估很可能是由于磷酸化的[Ca2+]敏感性略有增加，因为具有改变的磷酸化[Ca2+]敏感性的模型更准确地预测了由此产生的舒张。当猪颈动脉短暂拉伸或缩短然后恢复到原始长度时，其舒张的时间进程没有实质性改变。由于拉伸会使横桥分离，我修改了基于水母发光蛋白的闩锁桥模型以考虑拉伸诱导的横桥分离。由于拉伸前后[Ca2+]值略高于静息值，该模型预测磷酸化的横桥可以重新附着、去磷酸化并形成新的闩锁桥。该模型预测了舒张，除了在拉伸后的最初几秒钟。这些结果表明，闩锁桥重新附着对于解释舒张过程中对拉伸的大部分反应并非必要。舒张的限速步骤似乎是[Ca2+]的去除而不是闩锁桥的分离。
