Altered functional coupling of coronary K+ channels in diabetic dyslipidemic pigs is prevented by exercise.
Altered functional coupling of coronary K+ channels in diabetic dyslipidemic pigs is prevented by exercise.
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DOI：
10.1152/japplphysiol.00972.2002
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发表时间：
2003-09
影响因子：
3.3
通讯作者：
E. Mokelke;Q. Hu;M. Song;L. Toro;Hanumanth K. Reddy;Michael Sturek
中科院分区：
文献类型：
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作者：
E. Mokelke;Q. Hu;M. Song;L. Toro;Hanumanth K. Reddy;Michael Sturek
慢性高血糖和高胆固醇血症已被证明改变了血管平滑肌的离子电流。我们验证了一种假设，即高血糖和高脂血症(糖尿病血脂异常)的共同作用会增加钙敏感钾电流(KCA)，作为对细胞内钙浓度增加的代偿反应。我们还假设，运动训练可以防止KCA电流的这种升高。将小型尤卡坦猪随机分为5组：对照组、标准猪组(C，n=6)、高脂高脂组(H，n=5)、糖尿病标准猪组(D，n=7)、糖尿病高脂组(DD，n=12)和运动训练组(DDX，n=9)。高脂饲料由标准小型猪饲料添加胆固醇(2%)和椰子油组成。在体内和体外评估的DD患者的冠状动脉血管收缩增加通过运动来预防。膜片钳实验显示，在-10 mV到40 mV之间，H、D和DD组的K+电流密度高于DDX组。在Fura 2负载的细胞中，咖啡因诱导的钙释放激活电流在H、D和DD比C和DDX更大(P<；0.05)，而细胞内钙浓度在不同组之间没有差异。最后，Kca和Kv通道蛋白含量在组间没有差异。这些数据表明，高血糖、高脂血症和糖尿病血脂异常导致全细胞K+电流升高，Kca和Ca~(2+)释放功能偶联增加。耐力运动可阻止糖尿病血脂异常时钙离子释放与Kca通道激活的偶联增加。
Chronic hyperglycemia and hypercholesterolemia have been shown to alter ionic currents in vascular smooth muscle. We tested the hypothesis that the combined effect of hyperglycemia and hyperlipidemia (diabetic dyslipidemia) would increase the Ca2+-sensitive K+ (KCa) current as a compensatory response to an increase in intracellular Ca2+ concentration. We also hypothesized that exercise training would prevent this elevation in KCa current. Miniature Yucatan swine were randomly assigned to five groups: control, standard pig chow (C, n = 6); hyperlipidemic, high-fat pig chow (H, n = 5); diabetic, standard pig chow (D, n = 7); diabetic, high-fat pig chow ("diabetic dyslipidemic," DD, n = 12); and exercise-trained DD (DDX, n = 9). High-fat chow consisted of standard minipig chow supplemented with cholesterol (2%) and coconut oil. Increased coronary vasoconstriction assessed in vivo and in vitro in DD was prevented by exercise. Patch-clamp experiments performed on right coronary artery smooth muscle cells resulted in greater K+ current densities in the H, D, and DD groups vs. the DDX group between -10 and 40 mV. In fura 2-loaded cells, current activated by caffeine-induced Ca2+ release was greater in H, D, and DD compared with C and DDX (P < 0.05), whereas intracellular Ca2+ concentration was not different across groups. Finally, there were no differences in the KCa or Kv channel protein content between groups. These data indicate that hyperglycemia, hyperlipidemia, and diabetic dyslipidemia lead to elevated whole cell K+ current and increased functional coupling of KCa and Ca2+ release. Endurance exercise prevented increased coupling of Ca2+ release to KCa channel activation in diabetic dyslipidemia.