Reduced length-dependent cross-bridge recruitment in skinned fiber preparations of human failing myocardium
Reduced length-dependent cross-bridge recruitment in skinned fiber preparations of human failing myocardium
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DOI：
10.1007/s00421-002-0782-2
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发表时间：
2003-05-01
影响因子：
3
通讯作者：
Schwinger, RHG
中科院分区：
文献类型：
--
作者：
Brixius, K;Savidou-Zaroti, P;Schwinger, RHG
在人衰竭心肌中，肌球蛋白ATP酶活性被抑制。由于跨桥动力学的改变可能同时影响心脏收缩和舒张功能，本研究同时研究了人非衰竭的Triton X皮肤纤维制备物中的Ca 2+依赖性张力和肌动球蛋白ATP酶活性（MYO）。（供体心脏，n = 8）和失败（扩张型心肌病，n = 11）肌节长度增加的左心室心肌（1.9和2.1 μ m，α-辅肌动蛋白染色）。MYO/张力比作为表征肌原纤维能量学的参数进行分析。在肌节长度为1.9妈妈，Ca 2+的张力敏感性显着增加，在人类失败相比，非失败的心肌。在人类非衰竭心肌中，最大Ca 2+激活张力[1.9 pm vs. 2.1 mum，23.7（1.9）vs. 28.3（1.9）mN/mm（2）]和张力的Ca 2+敏感性[EC（5）0 Ca（2+）. (pCa)：5.67（0.06）vs. 7.07（0.11）]随着肌节长度的增加而增加。这伴随着Ca 2+依赖性MYO [+72（11）vs. +101（9）μ M ADP/s]的增强以及MYO的Ca 2+敏感性的增加[EC 50 Ca 2+（pCa）：5.84（0.08）vs. 6.86（0.08）]。在人衰竭心肌中，只有张力的Ca ~（2+）敏感性增加（而MYO不增加）。在失效组织与非失效组织中，张力成本增加[1.9 μ m：4.18（0.06）vs.3.53 2（0.06）（mN.s）/（mm（2）μ M ADP）; 2.1 μ m：4.28（0.13）vs.3.52（0.05）（mN.s）/（mm（2）μ M ADP）]。我们得出的结论是，在人类心肌衰竭，长度依赖性的力量产生可能会钝化，由于已经增加的钙离子亲和力的肌钙蛋白C，以及长度依赖性跨桥招聘的损害。
A depressed activity of myosin ATPase has been described in human failing myocardium. Since alterations in cross-bridge kinetics may affect both systolic and diastolic cardiac function, the present study simultaneously investigated Ca2+-dependent tension and actomyosin ATPase activity (MYO) in triton X-skinned fiber preparations of human non-failing (donor hearts, n = 8) and failing (dilated cardiomyopathy, n = 11) left ventricular myocardium at increasing sarcomeric length (1.9 and 2.1 mum, alpha-actinin staining). The MYO/tension ratio was analyzed as a parameter characterizing myofibrillar energetics. At a sarcomere length of 1.9 mum, the Ca2+ sensitivity of tension was significantly increased in human failing compared to non-failing myocardium. In human non-failing myocardium, maximal Ca2+-activated tension [1.9 pm vs. 2.1 mum, 23.7 (1.9) vs. 28.3 (1.9) mN/mm(2)] and the Ca2+ sensitivity of tension [EC(5)0Ca(2+). (pCa): 5.67 (0.06) vs. 7.07 (0.11)] were increased by increasing sarcomere length. This was accompanied by an enhancement in Ca2+-dependent MYO [+72 (11) vs. +101 (9) muM ADP/s] as well as an increase in the Ca2+-sensitivity of MYO [EC50Ca2+ (pCa): 5.84 (0.08) vs. 6.86 (0.08)]. In human failing myocardium, only Ca2+ sensitivity of tension (but not of MYO) increased. Tension cost was increased in failing vs. non-failing tissue [1.9 mum: 4.18 (0.06) vs. 3.53 2 (0.06) (mN.s)/(mm(2).muM ADP); 2.1 mum: 4.28 (0.13) vs. 3.52 (0.05) (mN.s)/(mm(2).muM ADP)]. We concluded that, in human failing myocardium, the length-dependent force generation may be blunted due to an already increased Ca2+-affinity of troponin C as well as an impairment of length-dependent cross-bridge recruitment.