Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Cell Metab. 2010 Jan;11(1):58-69. doi: 10.1016/j.cmet.2009.11.009.
Metabolic processes that regulate muscle energy use are major determinants of bodily energy balance. Here, we find that sarcolemmal ATP-sensitive K(+) (K(ATP)) channels, which couple membrane excitability with cellular metabolic pathways, set muscle energy expenditure under physiological stimuli. Disruption of K(ATP) channel function provoked, under conditions of unaltered locomotor activity and blood substrate availability, an extra energy cost of cardiac and skeletal muscle performance. Inefficient fuel metabolism in K(ATP) channel-deficient striated muscles reduced glycogen and fat body depots, promoting a lean phenotype. The propensity to lesser body weight imposed by K(ATP) channel deficit persisted under a high-fat diet, yet obesity restriction was achieved at the cost of compromised physical endurance. Thus, sarcolemmal K(ATP) channels govern muscle energy economy, and their downregulation in a tissue-specific manner could present an antiobesity strategy by rendering muscle increasingly thermogenic at rest and less fuel efficient during exercise.
调节肌肉能量利用的代谢过程是身体能量平衡的主要决定因素。在这里，我们发现肌浆膜 ATP 敏感性 K(+) (K(ATP)) 通道将膜兴奋性与细胞代谢途径联系起来，在生理刺激下设定肌肉能量消耗。在运动活动和血液底物可用性不变的情况下，破坏 K(ATP) 通道功能会引起心脏和骨骼肌性能的额外能量消耗。在 K(ATP) 通道缺陷的横纹肌中，燃料代谢效率低下会减少糖原和脂肪体储存，促进瘦体型。K(ATP) 通道缺陷引起的体重减轻倾向在高脂肪饮食下仍然存在，但通过降低身体耐力来实现肥胖限制。因此，肌浆膜 K(ATP) 通道控制肌肉能量经济性，其在组织特异性下调可能是一种抗肥胖策略，使肌肉在休息时更具产热能力，在运动时燃料效率更低。
