Karaki H
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
Nihon Yakurigaku Zasshi. 1990 Dec;96(6):289-99. doi: 10.1254/fpj.96.6_289.
Simultaneous measurements of cytoplasmic Ca2+ level [( Ca2+]i) and muscle contraction in smooth muscle indicated that [Ca2+]i gradually decreases during sustained contraction. This time-dependent dissociation has been explained by the latch bridge hypothesis, positive cooperativity between phosphorylated and non-phosphorylated crossbridges, involvement of cytoskeleton phosphorylation, or connection between myosin and actin filaments by caldesmon. Furthermore, it has been found that receptor agonists induce greater contraction than high K+ for a given increase in [Ca2+]i. This stimulus-dependent dissociation may be due to the receptor agonists-induced activation of protein kinase C which in turn decreases the inhibitory effect of calponin on the actin-myosin interaction, resulting in an apparent Ca2+ sensitization. Thus, the contractions induced by receptor agonists are due not only to the increase in [Ca2+]i but also to the increase in Ca2+ sensitivity of contractile elements. Ca2+ channel blockers inhibit the increase in [Ca2+]i but not the Ca2+ sensitization, and this may be the reason why these blockers are relatively weak inhibitors of the contraction induced by receptor agonists. By contrast, cyclic AMP and cyclic GMP decrease the Ca2+ sensitivity of contractile elements in addition to their effects to decrease [Ca2+]i.
对平滑肌细胞质钙离子水平[Ca2+]i和肌肉收缩的同步测量表明，在持续收缩过程中[Ca2+]i逐渐降低。这种时间依赖性解离已通过闩锁桥假说、磷酸化和非磷酸化横桥之间的正协同作用、细胞骨架磷酸化的参与或钙调蛋白介导的肌球蛋白与肌动蛋白丝之间的连接来解释。此外，已经发现，对于给定的[Ca2+]i升高，受体激动剂比高钾诱导更强的收缩。这种刺激依赖性解离可能是由于受体激动剂诱导蛋白激酶C激活，进而降低了钙调蛋白对肌动蛋白-肌球蛋白相互作用的抑制作用，导致明显的钙离子敏化。因此，受体激动剂诱导的收缩不仅归因于[Ca2+]i的升高，还归因于收缩元件对钙离子敏感性的增加。钙离子通道阻滞剂抑制[Ca2+]i的升高，但不抑制钙离子敏化，这可能是这些阻滞剂对受体激动剂诱导的收缩抑制作用相对较弱的原因。相比之下，环磷酸腺苷和环磷酸鸟苷除了降低[Ca2+]i的作用外，还降低收缩元件对钙离子的敏感性。
