Myofibrillar calcium sensitivity of isometric tension is increased in human dilated cardiomyopathies: role of altered beta-adrenergically mediated protein phosphorylation.
Myofibrillar calcium sensitivity of isometric tension is increased in human dilated cardiomyopathies: role of altered beta-adrenergically mediated protein phosphorylation.
复制标题
人类扩张型心肌病中肌原纤维钙对等长张力的敏感性增加：β-肾上腺素能介导的蛋白质磷酸化改变的作用。
DOI：
10.1172/jci118762
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Mentzer,RM
中科院分区：
文献类型：
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作者：
Wolff,MR;Buck,SH;Stoker,SW;Greaser,ML;Mentzer,RM
为了研究肌原纤维功能改变在人类扩张型心肌病中的作用，我们测定了在心脏移植或左心室辅助装置植入期间从9名扩张型心肌病（DCM）患者的左心室活检中获得的透化肌细胞大小的肌原纤维制剂（n = 16）的等长张力-钙关系。从用于心脏移植的6个正常心脏获得类似的制备物（n = 10）。两组的被动和最大Ca 2+激活张力相似。然而，与非衰竭制剂相比，DCM中等长张力的钙敏感性增加（[Ca 2 +]50=2.46+/-0.49 microM vs 3.24+/-0.51 microM，P < 0.001）。在体外治疗与蛋白激酶A（PKA）的催化亚基降低钙敏感性的张力在更大程度上失败比正常的准备。此外，PKA治疗后，失败和正常肌原纤维准备的等长张力-钙关系相似。这些研究结果表明，增加钙敏感性的等长张力扩张型心肌病可能至少部分是由于减少β-肾上腺素介导的（PKA依赖）磷酸化的肌原纤维调节蛋白，如肌钙蛋白I和/或C-蛋白。
To examine the role of alterations in myofibrillar function in human dilated cardiomyopathies, we determined isometric tension-calcium relations in permeabilized myocytesized myofibrillar preparations (n = 16) obtained from left ventricular biopsies from nine patients with dilated cardiomyopathy (DCM) during cardiac transplantation or left ventricular assist device implantation. Similar preparations (n = 10) were obtained from six normal hearts used for cardiac transplantation. Passive and maximal Ca2+-activated tensions were similar for the two groups. However, the calcium sensitivity of isometric tension was increased in DCM compared to nonfailing preparations ([Ca2+]50=2.46+/-0.49 microM vs 3.24+/-0.51 microM, P < 0.001). In vitro treatment with the catalytic subunit of protein kinase A (PKA) decreased calcium sensitivity of tension to a greater degree in failing than in normal preparations. Further, isometric tension-calcium relations in failing and normal myofibrillar preparations were similar after PKA treatment. These findings suggest that the increased calcium sensitivity of isometric tension in DCM may be due at least in part to a reduction of the beta-adrenergically mediated (PKA-dependent) phosphorylation of myofibrillar regulatory proteins such as troponin I and/or C-protein.