Differential effect of DPI 201-106 on the sensitivity of the myofilaments to Ca2+ in intact and skinned trabeculae from control and myopathic human hearts.

Differential effect of DPI 201-106 on the sensitivity of the myofilaments to Ca2+ in intact and skinned trabeculae from control and myopathic human hearts.
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DPI 201-106 对对照和肌病人类心脏的完整和带皮小梁中肌丝对 Ca2+ 敏感性的不同影响。

DOI:
10.1172/jci113769
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发表时间:
1988
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Morgan,JP
Morgan,JP
中科院分区:
--
文献类型:
--
作者:
Hajjar,RJ;Gwathmey,JK;Briggs,GM;Morgan,JP

文献摘要

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DPI,一种新的正性肌力药物,在来自对照组和肌病患者心脏的肌小梁中进行了比较,肌小梁装载了水母发光蛋白,一种生物发光钙指示剂,当它与钙结合时会发光,并在来自相同心脏的皂化皮肤肌小梁中进行了比较。力-pCa曲线在皂苷皮肤的纤维和峰力-峰Ca 2+曲线在水母发光蛋白负载的制剂之间的控制和肌病组织没有显着差异。来自相同对照心脏的去皮和负载水母发光蛋白的制剂中的力-pCa曲线显示随着DPI的加入没有显著的变化。相反,DPI存在下,在来自肌病心脏的水母发光蛋白负载和去皮肌肉中,力-钙关系存在显著变化,表明肌丝对钙的敏感性增加。肌病组织和对照组织之间钙激活调节的这些差异表明,药物可能在正常和患病心脏中产生不同的作用。
The effects of DPI, a new inotropic agent, were compared in trabeculae carneae from control and myopathic human hearts loaded with aequorin, a bioluminescent calcium indicator that emits light when it combines with calcium, and in saponin-skinned trabeculae carneae from the same hearts. The force-pCa curves in saponin-skinned fibers and the peak force-peak Ca2+ curves in aequorin-loaded preparations were not significantly different between the control and myopathic tissues. The force-pCa curve in the skinned and aequorin-loaded preparations from the same control hearts displayed no significant shifts with the addition of DPI. In contrast, a leftward shift was present in the force-calcium relationship in the presence of DPI in aequorin-loaded and skinned muscles from myopathic hearts, indicating an increase in the sensitivity of the myofilaments to calcium. These differences in the modulation of calcium activation between myopathic and control tissues indicate that pharmacological agents may produce differential effects in normal and diseased hearts.Images