Defective intracellular Ca2+ signaling contributes to cardiomyopathy in Type 1 diabetic rats
Defective intracellular Ca2+ signaling contributes to cardiomyopathy in Type 1 diabetic rats
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DOI：
10.1152/ajpheart.00313.2002
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发表时间：
2002-10-01
影响因子：
4.8
通讯作者：
Matlib, MA
中科院分区：
文献类型：
--
作者：
Choi, KM;Zhong, Y;Matlib, MA
本研究旨在探讨链脲佐菌素（STZ）诱导的糖尿病大鼠心肌病是否与细胞内Ca 2+信号转导缺陷有关。心脏收缩和舒张功能的抑制从糖尿病大鼠活体追踪到分离的单个心肌细胞。心肌细胞收缩和舒张的抑制与细胞内游离Ca ~（2+）浓度（[Ca ~（2+）]（i））的上升和下降的抑制是平行的。糖尿病大鼠肌细胞肌浆网（SR）Ca 2+储存以及Ca 2+释放和重新分配到SR的速率均受到抑制。Ca ~（2+）通过肌膜Na ~+/Ca ~（2+）交换器流出的速率也被抑制。然而，没有变化的电压依赖性L型钙通道电流触发钙释放SR。SR功能的抑郁症与SR钙ATP酶和兰尼碱受体蛋白减少和增加总的和非磷酸化受磷蛋白。Na+/Ca ~（2+）交换体活性的降低与其蛋白水平的降低有关。因此，可以得出结论，在STZ诱导的糖尿病大鼠中，由调节[Ca 2 +]（i）的蛋白质的表达和功能的改变引起的细胞内Ca 2+信号传导的缺陷有助于心肌病。受磷蛋白增加，Na+/Ca 2+交换减少，L型Ca 2+通道活性不变，在糖尿病心肌病模型中与其他类型的心肌病不同。
The goal of the study was to determine whether defects in intracellular Ca2+ signaling contribute to cardiomyopathy in streptozotocin (STZ) induced diabetic rats. Depression in cardiac systolic and diastolic function was traced from live diabetic rats to isolated individual myocytes. The depression in contraction and relaxation in myocytes was found in parallel with depression in the rise and decline of intracellular free Ca2+ concentration ([Ca2+](i)). The sarcoplasmic reticulum (SR) Ca2+ store and rates of Ca2+ release and resequestration into SR were depressed in diabetic rat myocytes. The rate of Ca2+ efflux via sarcolemmal Na+/Ca2+ exchanger was also depressed. However, there was no change in the voltage-dependent L-type Ca2+ channel current that triggers Ca2+ release from the SR. The depression in SR function was associated with decreased SR Ca2+-ATPase and ryanodine receptor proteins and increased total and nonphosphorylated phospholamban proteins. The depression of Na+/Ca2+ exchanger activity was associated with a decrease in its protein level. Thus it is concluded that defects in intracellular Ca2+ signaling caused by alteration of expression and function of the proteins that regulate [Ca2+](i) contribute to cardiomyopathy in STZ-induced diabetic rats. The increase in phospholamban, decrease in Na+/Ca2+ exchanger, and unchanged L-type Ca2+ channel activity in this model of diabetic cardiomyopathy are distinct from other types of cardiomyopathy.