ATP-sensitive K+ channel knockout compromises the metabolic benefit of exercise training, resulting in cardiac deficits
ATP-sensitive K+ channel knockout compromises the metabolic benefit of exercise training, resulting in cardiac deficits
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DOI：
10.2337/diabetes.53.suppl_3.s169
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发表时间：
2004-12-01
期刊：
影响因子：
7.7
通讯作者：
Terzic, A
中科院分区：
文献类型：
--
作者：
Kane, GC;Behfar, A;Terzic, A
运动训练会引起新陈代谢和心血管反应，这是健身的基础。协调这种适应性反应并确保在有计划的训练计划中获得广泛收益的分子机制尚不清楚。应激反应敏感的K+通道(K-ATP通道)由Kir6.2孔和磺脲受体结合而成，具有代谢敏感能力和广泛的组织表达，是整合系统对重复运动的适应性反应的潜在候选者。在这里，我们比较了缺乏功能性Kir6.2-K-ATP通道(Kir6.2-KO)的小鼠和野生型对照小鼠在28天耐力游泳方案下的反应。虽然慢性水上训练导致更轻、更瘦、更健康的野生动物，但Kir6.2-KO在运动能力方面表现出较少的增强，在体脂组成和血糖处理方面缺乏代谢改善和心肌细胞缺陷。此外，游泳的重复应激暴露了Kir6.2-KO的一个生存劣势，与心脏钙依赖的病理性结构损伤和心脏功能受损有关。因此，含有Kir6.2的K-ATP通道活性是实现无损伤运动训练的生理益处所必需的。
Exercise training elicits a metabolic and cardiovascular response that underlies fitness. The molecular mechanisms that orchestrate this adaptive response and secure the wide-ranging gains of a regimented exercise program are poorly understood. Formed through association of the Kir6.2 pore and the sulfonylurea receptor, the stress-responsive ATP-sensitive K+ channels (K-ATP channels), with their metabolic-sensing capability and broad tissue expression, are potential candidates for integrating the systemic adaptive response to repetitive exercise. Here, the responses of mice lacking functional Kir6.2-containing K-ATP channels (Kir6.2-KO) were compared with wild-type controls following a 28-day endurance swimming protocol. While chronic aquatic training resulted in lighter, leaner, and fitter wild-type animals, the Kir6.2-KO manifested less augmentation in exercise capacity and lacked metabolic improvement in body fat composition and glycemic handling with myocellular defects. Moreover, the repetitive stress of swimming unmasked a survival disadvantage in the Kir6.2-KO, associated with pathologic calcium-dependent structural damage in the heart and impaired cardiac performance. Thus, Kir6.2-containing K-ATP channel activity is required for attainment of the physiologic benefits of exercise training without injury.