Haworth R A, Nicolaus A, Goknur A B, Berkoff H A
Department of Surgery, University of Wisconsin Clinical Science Center, Madison 53792.
J Mol Cell Cardiol. 1988 Sep;20(9):837-46. doi: 10.1016/s0022-2828(88)80008-7.
We tested the hypothesis that isolated adult rat heart cells could be depleted of most of their ATP without undergoing contracture. Two strategies for ATP depletions were employed. First, cells were exposed to a high level of rotenone plus FCCP. The cells lost 90% of their ATP within 3 min without change in sarcomere length before undergoing contracture. Even though ATP levels were so low, glycolysis from glycogen was maximally activated at this time. Second, cells exposed to repeated cycles of acidic anoxia were depleted of 77% of their ATP without change in sarcomere length and remained rod-shaped when restored to normoxia and neutral pH. The hypothesis was thus confirmed. The results support the previously developed concept that ATP decline in cells can be synchronous, with a similar decline in all cells, or asynchronous, with a sudden decline in different cells at different times. Whether the decline is synchronous or asynchronous depends on the conditions of metabolic impairment. This concept can explain the pattern of ATP decline observed in whole hearts during ischemia, and also the mechanism by which glycolytic ATP appears to protect against contracture.
我们验证了一个假设，即分离的成年大鼠心脏细胞在不发生挛缩的情况下，其大部分ATP可被耗尽。采用了两种耗尽ATP的策略。首先，将细胞暴露于高水平的鱼藤酮加羰基氰化物-对-三氟甲氧基苯腙（FCCP）中。细胞在3分钟内失去了90%的ATP，在发生挛缩前肌节长度没有变化。尽管ATP水平很低，但此时糖原的糖酵解被最大程度地激活。其次，暴露于反复的酸性缺氧循环中的细胞，其ATP被耗尽了77%，肌节长度没有变化，恢复到常氧和中性pH值时仍保持杆状。因此该假设得到了证实。这些结果支持了先前提出的概念，即细胞内ATP的下降可以是同步的，所有细胞中都有类似的下降，也可以是异步的，不同细胞在不同时间突然下降。下降是同步还是异步取决于代谢损伤的条件。这一概念可以解释在缺血期间整个心脏中观察到的ATP下降模式，也可以解释糖酵解ATP似乎防止挛缩的机制。
