Changes in cardiac contractility related to calcium-mediated changes in phosphorylation of myosin-binding protein C
Changes in cardiac contractility related to calcium-mediated changes in phosphorylation of myosin-binding protein C
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DOI：
10.1016/s0006-3495(01)75765-7
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发表时间：
2001-08-01
影响因子：
3.4
通讯作者：
Winegrad, S
中科院分区：
文献类型：
--
作者：
McClellan, G;Kulikovskaya, I;Winegrad, S
钙离子可以通过激活特异性磷酸化肌原纤维蛋白肌球蛋白结合蛋白C（MyBP-C）和肌球蛋白调节轻链（RLC）的激酶来影响心肌收缩。为了研究钙调节的MyBP-C磷酸化对收缩的可能作用，将分离的静止和节律性收缩的心脏小梁暴露于不同浓度的细胞外钙，然后化学剥皮以夹紧收缩系统。在静止细胞中测量最大Ca激活力（F-max），所述静止细胞浸泡在1）2.5mM Ca中120分钟，2）1.25mM Ca中120分钟，或3）1.25mM Ca中120分钟，然后在7.5mM中10分钟，和4）细胞在2.5mM中节律性收缩20分钟。24.7和32.6 mN/mm（2）。F-max的变化与MyBP-C磷酸化程度的变化密切相关，并发生在细胞内Ca浓度低于与RLC磷酸化相关的水平。在β-肾上腺素能刺激产生额外的磷酸化之前，Ca调节激酶对MyBP-C的单磷酸化是必需的。这些结果表明MyBP-C的Ca依赖性磷酸化通过改变粗丝结构来调节收缩性。
Ca ions can influence the contraction of cardiac muscle by activating kinases that specifically phosphorylate the myofibrillar proteins myosin-binding protein C (MyBP-C) and the regulatory light chain of myosin (RLC). To investigate the possible role of Ca-regulated phosphorylation of MyBP-C on contraction, isolated quiescent and rhythmically contracting cardiac trabeculae were exposed to different concentrations of extracellular Ca and then chemically skinned to clamp the contractile system. Maximum Ca-activated force (F-max) was measured in quiescent cells soaking in 1) 2.5 mM Ca for 120 min, 2) 1.25 mM for 120 min, or 3) 1.25 mM for 120 min followed by 10 min in 7.5 mM, and 4) cells rhythmically contracting in 2.5 mM for 20 min. F-max was, respectively, 21.5, 10.5, 24.7, and 32.6 mN/mm(2). Changes in F-max. were closely associated with changes in the degree of phosphorylation of MyBP-C and occurred at intracellular concentrations of Ca below levels associated with phosphorylation of RLC. Monophosphorylation of MyBP-C by a Ca-regulated kinase is necessary before beta -adrenergic stimulation can produce additional phosphorylation. These results suggest that Ca-dependent phosphorylation of MyBP-C modulates contractility by changing thick filament structure.