Scott Kyle, Benkhalti Maria, Calvert Nicholas D, Paquette Mathieu, Zhen Li, Harper Mary-Ellen, Al-Dirbashi Osama Y, Renaud Jean-Marc
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Am J Physiol Cell Physiol. 2016 Oct 1;311(4):C559-C571. doi: 10.1152/ajpcell.00137.2015. Epub 2016 Aug 3.
The skeletal muscle ATP-sensitive K (K) channel is crucial in preventing fiber damage and contractile dysfunction, possibly by preventing damaging ATP depletion. The objective of this study was to investigate changes in energy metabolism during fatigue in wild-type and inwardly rectifying K channel (Kir6.2)-deficient (Kir6.2) flexor digitorum brevis (FDB), a muscle that lacks functional K channels. Fatigue was elicited with one tetanic contraction every second. Decreases in ATP and total adenylate levels were significantly greater in wild-type than Kir6.2 FDB during the last 2 min of the fatigue period. Glycogen depletion was greater in Kir6.2 FDB for the first 60 s, but not by the end of the fatigue period, while there was no difference in glucose uptake. The total amount of glucosyl units entering glycolysis was the same in wild-type and Kir6.2 FDB. During the first 60 s, Kir6.2 FDB generated less lactate and more CO; in the last 120 s, Kir6.2 FDB stopped generating CO and produced more lactate. The ATP generated during fatigue from phosphocreatine, glycolysis (lactate), and oxidative phosphorylation (CO) was 3.3-fold greater in Kir6.2 than wild-type FDB. Because ATP and total adenylate were significantly less in Kir6.2 FDB, it is suggested that Kir6.2 FDB has a greater energy deficit, despite a greater ATP production, which is further supported by greater glucose uptake and lactate and CO production in Kir6.2 FDB during the recovery period. It is thus concluded that a lack of functional K channels results in an impairment of energy metabolism.
骨骼肌ATP敏感性钾（K）通道对于预防纤维损伤和收缩功能障碍至关重要，可能是通过防止破坏性的ATP耗竭来实现的。本研究的目的是调查野生型和内向整流钾通道（Kir6.2）缺陷型（Kir6.2）的趾短屈肌（FDB，一种缺乏功能性K通道的肌肉）在疲劳过程中的能量代谢变化。每隔一秒进行一次强直收缩来诱发疲劳。在疲劳期的最后2分钟内，野生型FDB中ATP和总腺苷酸水平的下降显著大于Kir6.2 FDB。在最初的60秒内，Kir6.2 FDB中的糖原消耗更大，但在疲劳期结束时并非如此，而葡萄糖摄取没有差异。进入糖酵解的葡萄糖基单位总量在野生型和Kir6.2 FDB中是相同的。在最初的60秒内，Kir6.2 FDB产生的乳酸较少，二氧化碳较多；在最后的120秒内，Kir6.2 FDB停止产生二氧化碳并产生更多乳酸。疲劳期间由磷酸肌酸、糖酵解（乳酸）和氧化磷酸化（二氧化碳）产生的ATP在Kir6.2 FDB中比野生型FDB高3.3倍。由于Kir6.2 FDB中的ATP和总腺苷酸明显较少，这表明Kir6.2 FDB尽管ATP产生量更大，但能量亏空更大，恢复期Kir6.2 FDB中更高的葡萄糖摄取、乳酸和二氧化碳产生进一步支持了这一点。因此得出结论，功能性K通道的缺乏导致能量代谢受损。
