Ziegelhöffer A, Ravingerová T, Styk J, Tribulová N, Volkovová K, Seboková J, Breier A
Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Diabetes Res Clin Pract. 1996 Jul;31 Suppl:S93-103. doi: 10.1016/0168-8227(96)01236-3.
Abundant information is now available about changes in subcellular organelles that are responsible for the impaired intracellular calcium homeostasis in diabetic cardiomyopathy. Some of these changes concern heart sarcolemma and include decrease in the following variables: calcium binding, influx of calcium through the L-type calcium channels, (Na,K)-ATPase activity and its affinity to sodium, Na(+)-Ca2+ exchange, H(+)-Na+ exchange, etc. Diabetic hearts also exhibited increased tolerance to calcium, but none of the above membrane perturbations were clearly identified as the source of this effect. The present study was undertaken in order to identify those alterations appearing in diabetes which are specific for the diabetic heart only. Our interest was focused on changes in sarcolemmal ATPase activities, particularly those of the (Na,K)-ATPase and its activation by increasing concentrations of sodium and potassium. Studies were performed in the acute (8 days) and chronic (63 days) phase of development of insulin-dependent diabetic cardiomyopathy. Wistar rats were made diabetic by administration of streptozotocin. To test the effect of excess calcium, the well-established model of calcium paradox was used. From the results obtained the following conclusions have been made: (a) diabetic hearts exceed normal hearts in their tolerance to calcium overload. In this respect the effect of chronic diabetes is more pronounced than the effect of acute diabetes; (b) the activities of sarcolemmal ATPases in diabetic hearts remain relatively well preserved. For this reason and with respect to modulation of calcium tolerance, the changes in specific properties of the ATPases, particularly those in the (Na,K)-ATPase, outweigh the importance of perturbations in their activities; (c) the enormous decrease in affinity of the (Na,K)-ATPase to sodium (increased K(m) value) monitored in calcium paradox in acute diabetic hearts was absolutely missing in "calcium-tolerant" chronic diabetic hearts. This observation pointed to a possible relation that may exist between the specific properties (Na,K)-ATPase adapted to work in chronic diabetic hearts and the enhanced calcium tolerance of those hearts; (d) the specific mechanism responsible for improved activation of the (Na,K)-ATPase by sodium and also partially responsible for potassium ions, which is clearly manifested in chronic diabetic hearts upon calcium paradox, still remains to be elucidated. Nevertheless, it could be assumed that the same mechanism may be also co-responsible for the enhanced tolerance of diabetic hearts to calcium.
现在有大量关于亚细胞器变化的信息，这些变化与糖尿病性心肌病中细胞内钙稳态受损有关。其中一些变化涉及心脏肌膜，包括以下变量的降低：钙结合、通过L型钙通道的钙内流、（钠，钾）-ATP酶活性及其对钠的亲和力、钠-钙交换、氢-钠交换等。糖尿病心脏对钙的耐受性也有所增加，但上述膜扰动均未被明确确定为这种效应的来源。本研究旨在确定糖尿病中仅在糖尿病心脏中出现的那些改变。我们的兴趣集中在肌膜ATP酶活性的变化上，特别是（钠，钾）-ATP酶的活性及其通过增加钠和钾浓度的激活。研究在胰岛素依赖型糖尿病性心肌病发展的急性期（8天）和慢性期（63天）进行。通过给予链脲佐菌素使Wistar大鼠患糖尿病。为了测试过量钙的影响，使用了成熟的钙反常模型。根据获得的结果得出以下结论：（a）糖尿病心脏对钙超载的耐受性超过正常心脏。在这方面，慢性糖尿病的影响比急性糖尿病的影响更明显；（b）糖尿病心脏中肌膜ATP酶的活性相对保持良好。因此，就钙耐受性的调节而言，ATP酶的特定性质的变化，特别是（钠，钾）-ATP酶的变化，比其活性的扰动更为重要；（c）在急性糖尿病心脏的钙反常中监测到的（钠，钾）-ATP酶对钠的亲和力大幅降低（米氏常数增加）在“耐钙”的慢性糖尿病心脏中完全不存在。这一观察结果表明，适应于在慢性糖尿病心脏中工作的（钠，钾）-ATP酶的特定性质与这些心脏增强的钙耐受性之间可能存在关系；（d）在钙反常时慢性糖尿病心脏中明显表现出的由钠改善（钠，钾）-ATP酶激活以及部分由钾离子激活的具体机制仍有待阐明。然而，可以假设相同的机制也可能共同导致糖尿病心脏对钙的耐受性增强。
