Metabolic basis of decreased transient outward K+ current in ventricular myocytes from diabetic rats.
Metabolic basis of decreased transient outward K+ current in ventricular myocytes from diabetic rats.
复制标题
糖尿病大鼠心室肌细胞瞬时外向 K 电流减少的代谢基础。
DOI：
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发表时间：
1996
影响因子：
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通讯作者：
G. Rozanski
中科院分区：
文献类型：
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作者：
Z. Xu;K. Patel;G. Rozanski
本研究旨在探讨链脲佐菌素诱导的实验性糖尿病早期心脏K+通道功能改变的机制。采用全细胞电压钳技术记录2 ~ 4周糖尿病大鼠和年龄匹配的对照组大鼠心室肌细胞瞬时外向（Ito）和内向整流（IK 1）钾电流。在基础记录条件下，在18 mM外部葡萄糖存在下，糖尿病大鼠心肌细胞中的Ito密度比对照组（+60 mV; P < 0.01）低约30%，而IK 1密度在组间无差异。当外部葡萄糖浓度降低到5 mM 4-6 h时，两组心肌细胞的基础Ito密度均未发生变化。为了进一步研究糖尿病大鼠心肌细胞中Ito密度降低的可能代谢基础，我们分别测试了三种影响心肌细胞底物利用的结构不同的化合物：胰岛素（0.1 μ M），二氯乙酸盐（1.5 mM）和L-肉碱（10 mM）。每种化合物在体外处理4-6小时的糖尿病大鼠的肌细胞中完全使Ito密度正常化。相同的药物对对照心肌细胞的Ito密度没有影响，两组细胞的IK 1也没有改变。这些数据提供了第一个证据，以支持这一假设，即有一个代谢的基础上，降低Ito密度在糖尿病大鼠心室肌细胞在早期阶段的这个模型。此外，我们的数据表明，在糖尿病心脏中，葡萄糖代谢抑制可能是Ito通道功能变化的关键因素，因为增加葡萄糖利用的药物在短时间内使Ito密度正常化。
The purpose of this study was to examine the mechanisms of alterations in cardiac K+ channel function in early stages of experimental diabetes mellitus induced by streptozotocin. Transient outward (Ito) and inward rectifier (IK1) K+ currents were recorded by the whole cell voltage-clamp technique in ventricular myocytes isolated from hearts of 2- to 4-wk diabetic and age-matched control rats. Ito density in myocytes from diabetic rats was approximately 30% less than control (at +60 mV; P < 0.01) under basal recording conditions in the presence of 18 mM external glucose, whereas IK1 density was not different between groups. When external glucose concentration was decreased to 5 mM for 4-6 h, basal Ito density was not changed in either group of myocytes. To further examine the possible metabolic basis of reduced Ito density in myocytes from diabetic rats, we separately tested three structurally different compounds that affect substrate utilization in cardiac myocytes: insulin (0.1 microM), dichloroacetate (1.5 mM), and L-carnitine (10 mM). Each compound completely normalized Ito density in myocytes from diabetic rats treated in vitro for 4-6 h. The same agents had no effect on Ito density in control myocytes, nor was IK1 altered in either group of cells. These data provide the first evidence to support the hypothesis that there is a metabolic basis for decreased Ito density in diabetic rat ventricular myocytes in early stages of this model. Furthermore, our data suggest that depressed glucose metabolism in the diabetic heart may be a key factor underlying changes in Ito channel function, because agents that increase glucose utilization normalize Ito density within a short time period.