Lee S L, Ostadalova I, Kolar F, Dhalla N S
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Manitoba, Canada.
Mol Cell Biochem. 1992 Feb 12;109(2):173-9. doi: 10.1007/BF00229773.
In order to examine the status of Ca2+ channels in heart sarcolemma during the development of diabetes, rats were injected intravenously with 65 mg/kg streptozotocin and hearts were removed 1, 3 and 8 weeks later. Crude membranes from the ventricular muscle were prepared and the specific binding of 3H-nitrendipine was studied by employing different concentrations of this Ca(2+)-antagonist. A significant decrease in both dissociation constant and maximal number of 3H-nitrendipine binding was observed in 3 and 8 weeks diabetic preparations. No such alterations were evident in diabetic brain membranes. Treatment of diabetic animals with insulin prevented the occurrence of these changes in the myocardium. The altered 3H-nitrendipine binding characteristics in diabetic heart membranes may not be due to the high levels of circulating catecholamines in this experimental model because no such changes were seen upon injecting a high dose (40 mg/kg) of isoproterenol in rats for 24 hr. The reduced number of 3H-nitrendipine binding sites may decrease Ca(2+)-influx through voltage sensitive Ca2+ channels and partly explain the depressed cardiac contractile force development in chronic diabetes whereas the increased affinity of Ca2+ channels may partly explain the increased sensitivity of diabetic heart to Ca2+.
为了研究糖尿病发展过程中心脏肌膜中钙通道的状态，给大鼠静脉注射65mg/kg链脲佐菌素，1、3和8周后取出心脏。制备心室肌的粗制膜，并通过使用不同浓度的这种钙拮抗剂研究3H-尼群地平的特异性结合。在糖尿病3周和8周的制剂中，观察到3H-尼群地平结合的解离常数和最大结合数均显著降低。在糖尿病动物的脑膜中未观察到这种改变。用胰岛素治疗糖尿病动物可防止心肌中出现这些变化。糖尿病心脏膜中3H-尼群地平结合特性的改变可能不是由于该实验模型中循环儿茶酚胺水平升高所致，因为给大鼠注射高剂量（40mg/kg）异丙肾上腺素24小时后未观察到这种变化。3H-尼群地平结合位点数量的减少可能会减少通过电压敏感性钙通道的钙内流，并部分解释慢性糖尿病时心脏收缩力发展的降低，而钙通道亲和力的增加可能部分解释糖尿病心脏对钙的敏感性增加。
