Lammerich A, Holzhütter H G, Janiak R, Storch E, Günther J
Institute of Physiology, Humboldt University, Berlin, Germany.
Gen Physiol Biophys. 1994 Oct;13(5):377-92.
The negative inotropic effect of 2,3-butanedione monoxime (BDM) on the isometric twitch of guinea-pig papillary muscle was analysed by parameters characterizing the time course of the mechanogram. BDM at concentrations of up to 4 mmol/l produced a clear negative inotropic effect, whereas the Ca transient measured in isolated cardiomyocytes was only slightly affected. Peak force was more reduced than dF/dtmax and dF/dtmin. This led to an earlier, more narrow peak and a shortening of twitch duration. Based on a reaction scheme for the cross-bridge cycle, a mathematical model using a Ca transient and mechanograms as input data has been developed. The kinetic parameters were estimated by fitting the model to various time courses of force obtained at rising concentrations of BDM. BDM decreased the ratio of rate constants for cross-bridge attachment and detachment in a concentration-dependent manner: the formation of cross-bridges became inhibited, whereas dissociation was promoted. Above 4 mmol/l BDM the more marked alterations of the parameters of the mechanogram indicated an additional suppressing effect on intracellular Ca supply. The computer analysis suggests how the cellular mechanism(s) of the BDM-induced negative inotropic effect are reflected in the time course of the mechanogram.
通过表征机械图时间进程的参数，分析了2,3 - 丁二酮一肟（BDM）对豚鼠乳头肌等长收缩的负性肌力作用。浓度高达4 mmol/L的BDM产生明显的负性肌力作用，而在分离的心肌细胞中测量的钙瞬变仅受到轻微影响。峰值力比dF/dtmax和dF/dtmin降低得更多。这导致峰值更早、更窄，并缩短了收缩持续时间。基于横桥循环的反应方案，开发了一种以钙瞬变和机械图作为输入数据的数学模型。通过将模型拟合到BDM浓度升高时获得的各种力的时间进程来估计动力学参数。BDM以浓度依赖的方式降低横桥附着和解离的速率常数之比：横桥的形成受到抑制，而解离则被促进。高于4 mmol/L的BDM时，机械图参数的更明显变化表明对细胞内钙供应有额外的抑制作用。计算机分析表明BDM诱导的负性肌力作用的细胞机制如何在机械图的时间进程中得到体现。
