Hasin Y, Doorey A, Barry W H
J Mol Cell Cardiol. 1984 Sep;16(9):823-34. doi: 10.1016/s0022-2828(84)80006-1.
The effects of inhibition of oxidative phosphorylation by 1 mM cyanide (CN) and of glycolysis by 20 mM 2-deoxyglucose (2DG) on contraction and relaxation of cultured monolayers of chick embryo heart cells were determined. Exposure to these agents first induced a gradual decline in contractility and a transient impairment of relaxation. Spontaneous beating then ceased, associated with increased relaxation, followed by a marked and prolonged contracture. This contracture was completely reversible after washout of metabolic inhibitors. The effects of calcium flux inhibitors on the time course of development of contracture were studied. Verapamil, which inhibits Ca influx via the slow Ca channel, delayed the onset of contracture when used in pretreatment, but had no effect if added to cultures after exposure to CN + 2DG. Lanthanum, which inhibits Ca influx both via the slow Ca channel and via Na-Ca exchange, delayed onset of contracture if added after exposure to CN and 2DG, but accelerated contracture if added prior to treatment with CN + 2DG. Cellular exchangeable calcium content, measured after exposure to CN and 2DG for the same time period that produced contracture, was reduced compared to the control level while unidirectional Ca influx rate was not measurably altered. Exchangeable Ca content was unaffected by pretreatment with verapamil and La, but was reduced if cells were exposed to La after metabolic inhibition. These findings suggest that after metabolic inhibition intracellular storage capacity for Ca+ is reduced in cultured heart cells. Ca influx via the slow Ca channel after metabolic inhibition does not appear to contribute to development of contracture in this model system. However, Ca entry via Na-Ca exchange may accelerate cellular contracture developing after metabolic inhibition of ATP production.
测定了1 mM氰化物（CN）抑制氧化磷酸化以及20 mM 2-脱氧葡萄糖（2DG）抑制糖酵解对鸡胚心脏细胞培养单层收缩和舒张的影响。暴露于这些试剂首先导致收缩性逐渐下降和舒张的短暂受损。然后自发搏动停止，伴有舒张增加，随后出现明显且持久的挛缩。在洗去代谢抑制剂后，这种挛缩是完全可逆的。研究了钙通量抑制剂对挛缩发展时间进程的影响。维拉帕米通过慢钙通道抑制钙内流，预处理时使用可延迟挛缩的发生，但在暴露于CN + 2DG后添加到培养物中则无作用。镧既通过慢钙通道又通过钠钙交换抑制钙内流，在暴露于CN和2DG后添加可延迟挛缩的发生，但在使用CN + 2DG处理前添加则会加速挛缩。在与产生挛缩相同的时间段暴露于CN和2DG后测量的细胞可交换钙含量与对照水平相比降低，而单向钙内流速率未显著改变。可交换钙含量不受维拉帕米和镧预处理的影响，但如果细胞在代谢抑制后暴露于镧则会降低。这些发现表明，在代谢抑制后，培养的心脏细胞中Ca +的细胞内储存能力降低。在该模型系统中，代谢抑制后通过慢钙通道的钙内流似乎对挛缩的发展没有贡献。然而，通过钠钙交换的钙内流可能会加速ATP产生代谢抑制后细胞挛缩的发展。
