Rotenone partially reverses decreased BKCa currents in cerebral artery smooth muscle cells from streptozotocin-induced diabetic mice
Rotenone partially reverses decreased BKCa currents in cerebral artery smooth muscle cells from streptozotocin-induced diabetic mice
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鱼藤酮部分逆转链脲佐菌素诱导的糖尿病小鼠脑动脉平滑肌细胞中 BKCa 电流的降低
DOI：
10.1111/j.1440-1681.2009.05222.x
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发表时间：
2009-10-01
影响因子：
2.9
通讯作者：
Gao, Feng
中科院分区：
文献类型：
--
作者：
Dong, Ling;Xie, Man-Jiang;Gao, Feng
活性氧（ROS）可引起糖尿病血管并发症并损害血管舒张功能.大电导钙激活钾通道（BKCa）调节血管张力，在血管收缩中发挥重要的负反馈作用。在本研究中，我们测试了ROS调节糖尿病脑动脉平滑肌细胞中BKCa功能的假设。通过注射链脲佐菌素（STZ; 180 mg/kg，i. p.，溶解在无菌盐水中）。对照组和糖尿病小鼠每隔一天用12.7 μ mol/L鱼藤酮（线粒体电子传递链复合物I的抑制剂）或安慰剂治疗5周。采用全细胞膜片钳技术和功能性血管舒张方法记录脑动脉平滑肌细胞BKCa电流和肌源性张力，结果显示：糖尿病组脑动脉平滑肌细胞自发性瞬时外向电流较对照组明显降低。尽管鱼藤酮治疗的糖尿病小鼠的电流仅适度增加，但它们仍显着低于对照组。此外，在糖尿病小鼠中降低的宏观BKCa电流在鱼藤酮治疗的糖尿病小鼠中部分恢复糖尿病小鼠大脑后动脉肌源性张力显著高于对照组，但这种受损的收缩在鱼藤酮治疗的糖尿病组中部分逆转糖尿病组小鼠脑动脉中H_2O_2浓度较对照组明显升高（P < 0.05）。结论：鱼藤酮部分逆转了STZ诱导的1型糖尿病小鼠BKCa电流的下降，这种逆转可能与鱼藤酮抑制H2 O2产生有关。活性氧，特别是H2 O2，是糖尿病脑动脉BKCa通道和肌源性张力的重要调节剂。
P>Reactive oxygen species (ROS) cause vascular complications and impair vasodilation in diabetes mellitus. Large-conductance Ca2+-activated potassium channels (BKCa) modulate vascular tone and play an important negative feedback role in vasoconstriction. In the present study, we tested the hypothesis that ROS regulate the function of BKCa in diabetic cerebral artery smooth muscle cells.Diabetes was induced in male BALB/c mice by injection of streptozotocin (STZ; 180 mg/kg, i.p., dissolved in sterile saline). Control and diabetic mice were treated with 12.7 mu mol/L rotenone, an inhibitor of the mitochondrial electron transport chain complex I, or placebo every other day for 5 weeks. The whole-cell patch clamp-technique and functional vasomotor methods were used to record BKCa currents and myogenic tone of cerebral artery smooth muscle cells.In the diabetic group, there was a significant decrease in spontaneous transient outward currents in cerebral artery smooth muscle cells compared with control. Although the currents were only moderately increased in rotenone-treated diabetic mice, they remained significantly lower than in the control group. Furthermore, the macroscopic BKCa currents that were decreased in diabetic mice were partially recovered in rotenone-treated diabetic mice (P < 0.05 vs untreated diabetic group).The posterior cerebral artery from diabetic mice had a significantly higher myogenic tone than the control group, but this impaired contraction was partially reversed in the rotenone-treated diabetic group (P < 0.05 vs untreated diabetic group).The H2O2 concentration was significantly increased in cerebral arteries from diabetic mice compared with control. This increase in H2O2 was significantly blunted by rotenone treatment.In conclusion, rotenone partially reverses the decreased macroscopic BKCa currents in STZ-induced Type 1 diabetic mice and this reversal of BKCa currents may be related to the inhibitory effects of rotenone on H2O2 production. Reactive oxygen species, particularly H2O2, are important regulators of BKCa channels and myogenic tone in diabetic cerebral artery.