Role of myosin heavy chain composition in kinetics of force development and relaxation in rat myocardium
Role of myosin heavy chain composition in kinetics of force development and relaxation in rat myocardium
复制标题
DOI：
10.1111/j.1469-7793.1998.171by.x
复制
发表时间：
1998-11-15
影响因子：
5.5
通讯作者：
Moss, RL
中科院分区：
文献类型：
--
作者：
Fitzsimons, DP;Patel, JR;Moss, RL
1. 在化学剥皮和完整的成年大鼠心肌制剂中，研究了心室肌球蛋白重链（MHC）组成对活化和松弛动力学的影响。甲状腺缺乏症诱导心室MHC异构体表达从正常甲状腺大鼠的80% α -MHC/20% β -MHC变为100% β -MHC，而不改变细丝相关调节蛋白的表达。在单皮肌细胞中，β - mhc表达的增加并没有显著影响最大Ca2+激活张力（P-0）或张力的Ca2+敏感性（pCa(50)）。然而，由于β - mhc表达增加，空载缩短速度（V-0）下降了80%。激活动力学和弛豫分别使用笼型Ca2+化合物DM-nitrophen和笼型Ca2+螯合剂重氮-2在剥皮的多细胞制剂中进行了研究。表达100% β - mhc的心肌表现出次极大张力和最大张力发展的明显速率（k(Ca)）比对照心肌低60%，从稳定的次极大力松弛的半时间增加了2倍。在有和没有β -肾上腺素能刺激（70 nM异丙肾上腺素（异丙肾上腺素））的活肌细胞中评估细胞缩短和细胞内Ca2+瞬态的时间过程。甲状腺缺乏对心肌细胞缩短程度、静息或峰值fura-2荧光比值均无影响。然而，甲状腺缺乏诱导β - mhc表达与肌细胞缩短和延长的一半时间增加以及fura-2荧光比衰减的一半时间增加有关。在没有和存在β -肾上腺素能刺激的情况下，尽管β -激动剂加速了抽搐和Ca2+瞬态的动力学，但定性的结果相似。总的来说，这些数据提供了证据，表明β - mhc表达的增加通过减缓力发展和力松弛的速度，显著促进了甲状腺功能不足心肌收缩功能的抑制。
1. The effects of ventricular myosin heavy chain (MHC) composition on the kinetics of activation and relaxation were examined in both chemically skinned and intact myocardial preparations from adult rats. Thyroid deficiency was induced to alter ventricular MHC isoform expression from similar to 80% alpha-MHC/20% beta-MHC in euthyroid rats to 100% beta-MHC, without altering the expression of thin-filament-associated regulatory proteins.2. In single skinned myocytes, increased expression of beta-MHC did not significantly affect either maximal Ca2+-activated tension (P-0) or the Ca2+ sensitivity of tension (pCa(50)). However, unloaded shortening velocity (V-0) decreased by 80% due to increased beta-MHC expression.3. The kinetics of activation and relaxation were examined in skinned multicellular preparations using the caged Ca2+ compound DM-nitrophen and caged Ca2+ chelator diazo-2, respectively. Myocardium expressing 100% beta-MHC exhibited apparent rates of submaximal and maximal tension development (k(Ca)) that were 60% lower than in control myocardium, and a 2-fold increase in the half-time for relaxation from steady-state submaximal force.4. The time courses of cell shortening and intracellular Ca2+ transients were assessed in living, electrically paced myocytes, both with and without beta-adrenergic stimulation (70 nM isoproterenol (isoprenaline)). Thyroid deficiency had no affect on either the extent of myocyte shortening or the resting or peak fura-2 fluorescence ratios. However, induction of beta-MHC expression by thyroid deficiency was associated with increased half-times for myocyte shortening and relengthening and increased half-time for the decay of the fura-2 fluorescence ratio. Qualitatively similar results were obtained in both the absence and the presence of beta-adrenergic stimulation although the beta-agonist accelerated the kinetics of the twitch and the Ca2+ transient.5. Collectively, these data provide evidence that increased beta-MHC expression contributes significantly to the observed depression of contractile function in thyroid deficient myocardium by slowing the rates of both force development and force relaxation.